Open Access

The possible association between AQP9 in the intestinal epithelium and acute liver injury‑induced intestinal epithelium damage

  • Authors:
    • Tianxin Xiang
    • Shanfei Ge
    • Jiangxiong Wen
    • Junfeng Xie
    • Lixia Yang
    • Xiaoping Wu
    • Na Cheng
  • View Affiliations

  • Published online on: October 10, 2018     https://doi.org/10.3892/mmr.2018.9542
  • Pages: 4987-4993
  • Copyright: © Xiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The present study aimed to investigate the expression and function of aquaporin (AQP)9 in the intestinal tract of acute liver injury rat models. A total of 20 Sprague Dawley rats were randomly divided into four groups: Normal control (NC) group and acute liver injury groups (24, 48 and 72 h). Acute liver injury rat models were established using D‑amino galactose, and the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (Tbil) and albumin were determined using an automatic biochemical analyzer. Proteins levels of myosin light chain kinase (MLCK) in rat intestinal mucosa were investigated via immunohistochemistry. Pathological features were observed using hematoxylin and eosin (H&E) staining. MLCK, AQP9 and claudin‑1 protein expression levels were detected via western blotting. Levels of ALT and AST in acute liver injury rats were revealed to steadily increase between 24 and 48 h time intervals, reaching a peak level at 48 h. Furthermore, TBil levels increased significantly until 72 h. Levels of ALT were revealed to significantly increase until the 48 h time interval, and then steadily decreased until the 72 h time interval. The acute liver injury 72 h group exhibited the greatest levels of MLCK expression among the three acute liver injury groups; however, all three acute liver injury groups exhibited enhanced levels of MLCK expression compared with the NC group. Protein levels of AQP9 and claudin‑1 were enhanced in the NC group compared with the three acute liver injury groups. H&E staining demonstrated that terminal ileum mucosal layer tissues obtained from the acute liver injury rats exhibited visible neutrophil infiltration. Furthermore, the results revealed that levels of tumor necrosis factor‑α, interleukin (IL)‑6 and IL‑10 serum cytokines were significantly increased in the acute liver injury groups. In addition, AQP9 protein expression was suppressed in acute liver injury rats, which induced pathological alterations in terminal ileum tissues may be associated with changes of claudin‑1 and MLCK protein levels.

Introduction

The major function of the intestinal epithelial barrier is to regulate the transport of molecules through transcellular and paracellular pathways between the hostile environment of the intestinal epithelium and the sub-epithelial tissue (1). The intestinal epithelial barrier has a selective permeable barrier that limits the permeation of luminal noxious molecules, including toxins, pathogens and antigens, while regulating the absorption of nutrients and water. This barrier is established by intercellular tight junction (TJ) structures (2). TJ assembly involves at least four types of transmembrane proteins: Tricellulin, claudins, occludin and junctional adhesion molecules. Claudins are structural proteins present in TJs and are involved in the regulation of paracellular movement by forming a barrier across the epithelial monolayer (3). Altered functions of claudins are associated with different forms of cancer, inflammatory bowel diseases and diarrhea (4). Claudin-1, a major structural and functional TJ protein is responsible for modulating the permeability of the epidermis (5).

Myosin light chain kinase (MLCK) is a calcium-dependent enzyme present in the cytoskeleton and the cytoplasm (6). MLCK may promote phosphorylation of the myosin light chain, which regulates the cytoskeleton (6). The MLCK pathway mediates intestinal epithelial barrier permeability by regulating TJs (7). A previous study revealed that downregulation of MLCK may attenuate damage to TJs (8). The results of the aforementioned studies suggest that MLCK has an important role in TJ damage under endotoxemic conditions.

Aquaporins (AQPs), including AQP0-AQP12, are a family of small integral membrane proteins that transport water across the cytoplasmic membrane. AQP9 is a subtype of the AQP protein family that is present in mammalian cells (9), and murine AQP9 protein expression has been demonstrated in liver, skin, epididymal, epidermal and neuronal cells (10,11). It has been well established that AQP9 functions as an aquaglyceroporin protein in the liver, facilitates hepatic uptake of glycerol (1214), and attenuates glaucomatous damage (15). AQP9 was first reported to be present in the duodenum, jejunum, ileum and colon (16) and a more recent study demonstrated that AQP9 has important roles in the digestive system (17). Therefore, AQP9 may have an important role in energy metabolism by functioning as channels in metabolic pathways.

The present study aimed to determine the association between AQP9 expression in the intestinal mucosa and conditions in which TJs are disrupted. This was investigated by comparing the expression levels of claudin-1 and MLCK; revealing the pathological features of ileum tissue in the normal control (NC) group, and acute liver injury groups at 2, 48, 72 h time intervals; and determining the association between the expression levels of AQP, Claudin-1 and MLCK.

Materials and methods

Materials

A total of 20 male Sprague Dawley rats (age, 3 months; body weight, 180–240 g), were purchased from the Department of Animal Science and Technology, Nanchang University (Nanchang, China). D-galactosamine was purchased from Shanghai Oripharm Co. Ltd. (Shanghai, China). Antibodies against claudin 1 (cat. no. 4933s; Cell Signaling Technology, Inc., Danvers, MA, USA), MLCK (cat. no. ab76092), AQP9 (cat. no. ab15129) and β-actin (cat. no. ab8228; all Abcam, Cambridge, UK) were used. An immunohistochemical staining kit was purchased from Nanjing KeyGen Biotech Co., Ltd. (Nanjing, China).

Establishment of an acute liver injury animal model and preparation of tissue specimens. All animal experiments were approved by the Animal Ethics Association of the First Affiliated Hospital of Nanchang University. Rats were housed in a specific pathogen-free environment at 23±2°C with 45–65% humidity and under a 12 h light/dark cycle. The animals had free access to food and water. The rats were randomly divided into two groups following one week of adaptive feeding: An acute liver injury group (15 rats) and a NC group (5 rats). Animal models of acute liver injury were established by one intraperitoneal injection of D-galactosamine (D-GalN; 1,200 mg/kg). A total of five animals were sacrificed at 24, 48 and 72 h time intervals post-injection. Rats in the NC group were subjected to intraperitoneal injection of normal saline (12 ml/kg) and then sacrificed at the 72 h time interval. Following this, serum, liver and ileum tissue specimens from all rats were collected for subsequent investigation.

Serum biochemical examination

Whole blood samples were centrifuged at a speed of 1,500 × g for 15 min at 4°C to separate the serum. Following this, levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (Tbil) and albumin (ALB) were detected in serum samples using an automatic biochemical analyzer (Beckman Coulter Chemistry Analyzer AU5800 Series; Beckman Coulter, Inc., Brea, CA, USA).

Pathological examination of liver and ileum tissues

Liver and ileal tissues (~0.5 g) were collected, washed with PBS, fixed in 10% neutral formaldehyde solution for 24 h at 4°C and then embedded in paraffin sections. The pathological alterations in liver and ileum tissue were observed under a light microscope (BX41; Olympus, Corporation, Tokyo, Japan), following hematoxylin and eosin staining for 5 min at room temperature. At least five fields of view were captured and analyzed.

Western blot analysis

The expression levels of MLCK, claudin-1 and AQP9 in terminal ileum tissues were detected via western blotting. The same weight (~30 mg) of terminal ileum tissue samples was obtained from rats belonging to each group and total protein was isolated using the illustra triplePrep kit (cat. no. 28-9425-44; GE Healthcare Life Sciences, Little Chalfont, UK). The bicinchoninic acid assay method (BCA Protein Assay kit; cat. no. P0011; Beyotime Institute of Biotechnology, Haimen, China) was used for the determination of protein concentration in the supernatant. Equal amounts of protein (20 µg) were loaded into lanes of 6 and 12% SDS-PAGE. Once the proteins had migrated through the gel, the current was terminated and gels were transferred to polyvinylidene difluoride (PVDF) membranes in transfer buffer at 18 V for 60 min. PVDF membranes were then blocked with 5% non-fat dry milk in Tris-buffered saline containing 0.1% Tween-20 at room temperature for 1 h. Membranes were incubated overnight at 4°C with primary antibodies against the following proteins: MLCK (1:250; cat. no. ab76092), AQP9 (1:250; cat. no. ab15129; both Abcam), claudin-1 (1:250; cat. no. 4933s; Cell Signaling Technology, Inc.) and β-actin (1:5,000; cat. no. ab8228; Abcam). Following this, membranes were incubated with horseradish peroxidase-conjugated goat anti-rabbit secondary antibodies (1:5,000; cat. no. ab6721; Abcam) for 2 h at room temperature. Membranes were subsequently washed three times with Tris-buffered saline containing 0.1% Tween-20 and proteins were then visualized using Pierce™ ECL Western Blotting Substrate (Pierce; Thermo Fisher Scientific, Inc., Waltham, MA, USA), according to the manufacturer's protocol. Each sample was normalized against β-actin expression. The protein bands were analyzed for densitometry using Quantity One software version 1.4.6 (Bio-Rad Laboratories, Inc., Hercules, CA, USA).

Immunohistochemistry (IHC)

IHC assays were performed to determine protein expression levels of claudin-1 and MLCK in terminal ileum tissues obtained from each group. Tissue sections (4 µm) were fixed with 10% neutral-buffered formalin for 24 h at 4°C and then embedded in paraffin. Paraffin sections were incubated for 2 h at 67°C and then subjected to dewaxing, boiling and washing with PBS. Following this, sections were incubated with rabbit anti-mouse monoclonal primary antibodies against MLCK (1:250; cat. no. ab76092; Abcam) for 60 min at room temperature, followed by incubation with anti-rabbit IgG horseradish peroxidase-linked antibody (1:200; cat. no. 7074; Cell Signaling Technology, Inc.) at 37°C for 15 min. Immunohistochemical staining was visualized by incubating sections with 3,3′-diaminobenzidine chromogen for 3 min at room temperature. A 50i Nikon Fluorescence Microscope (Nikon Corporation, Tokyo, Japan) and Adobe Photoshop CS4 software version 11.0 (Adobe Systems, Inc., San Jose, CA, USA) were used to capture and analyze the images. Finally, samples were counterstained with 1 mg/ml hematoxylin for 3 min at room temperature, dehydrated in alcohol and then mounted. Two investigators blinded to the clinical data, semi-quantitatively scored the slides by evaluating the staining intensity and percentage of stained cells in selected areas. At least five fields of view were captured at magnification ×200. The staining intensity was scored as 0 (no signal), 1 (weak), 2 (moderate), or 3 (high). The percentage of cells stained was scored as 1 (1–25%), 2 (26–50%), 3 (51–75%), or 4 (76–100%). A final score of 0–12 was obtained by multiplying the intensity and percentage scores (18).

ELISA

Expression levels of secreted tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10 in the supernatant were investigated using rat TNF-α (cat. no. ab100785), IL-6 (cat. no. ab100772) and IL-10 (cat. no. ab100765; all Abcam) ELISA kits according to the manufacturer's protocol. Absorbance values were determined using a Synergy HT Microplate Reader (BioTek Instruments, Inc., Winooski, VT, USA) at 450 nm, and IL-10 concentrations were calculated according to a standard curve and dilution ratio. All assays were performed in triplicate.

Statistical analysis

Statistical analysis was performed using SPSS software (version 19.0; IBM Corps., Armonk, NY, USA). Experiments were repeated six times and all data are expressed as the mean ± standard error of the mean. For statistical comparison of normal distributed data, a one-way analysis of variance followed by Tukey's post hoc test was used. P<0.05 was considered to indicate a statistically significant difference.

Results

Levels of serum biochemical markers in the NC and acute liver injury model groups

The results demonstrated that ALT and AST levels detected in rats in the acute liver injury groups increased in a time-dependent manner until the 48 h time interval; then were levels of ALT and AST were decreased at the 72 h time interval. The levels of Tbil were revealed to increase in a time-dependent manner, and the results also demonstrated that Alb levels were significantly reduced at the 72 h time interval (Table I). These results suggested that rats were suffering from acute liver damage (19). Compared with the NC group, differences regarding levels of ALT, AST and Tbil in acute liver injury groups were statistically significant compared with the (P<0.05; Table I).

Table I.

Comparative analysis of serum biochemical index levels in acute liver injury model rats at three time intervals and NC rats.

Table I.

Comparative analysis of serum biochemical index levels in acute liver injury model rats at three time intervals and NC rats.

GroupsRats (n)ALT (U/l)AST (U/l)Tbil (µmol/l)Alb (g/l)
NC526.67±5.03113.33±7.020.53±0.2123.33±1.79
M-24 h5 1,633.53±449.11a 3,472.67±314.42a 22.15±6.02a23.83±2.78
M-48 h5 3,886.64±255.62a 5,013.50±749.38a 60.47±11.74a21.50±1.89
M-72 h5 935.57±173.05a 2,230.75±297.13a 114.45±24.46a 20.88±2.38a

a P<0.05 vs. the NC group. M, model group; ALT, alanine aminotransferase; AST, aspartate aminotransferase; Tbil, total bilirubin; ALB, albumin; NC, normal control.

Pathological features of liver tissues obtained from rats in each group

The liver tissues obtained from rats in the NC group exhibited intact hepatic lobules, with the lobular central vein presented at the center and the hepatic cord radially arranged, in the absence of marked levels of inflammation, necrosis and degeneration (Fig. 1). The normal structure of liver tissues obtained from rats with acute liver injury at the 72 h time interval disappeared, with inflammatory cell infiltration, liver sinus congestion and hemorrhaging, and the liver cells displayed signs of necrosis (Fig. 1).

Pathological features of terminal ileum tissues in NC rats and acute liver injury rats

Complete mucosal structure was demonstrated in terminal ileum tissues obtained from NC rats, in the absence of inflammation, necrosis and shedding (Fig. 2). However, terminal ileum tissues obtained from rats belonging to the acute liver injury groups exhibited visibly increased levels of neutrophil infiltration in a time-dependent manner, enhanced levels of interstitial edema in mucosa and submucosa villi, and, at the 72 h time interval, part of the tip of the villi was eroded in the terminal ileum mucosa model 24, 48 and 72 h (Fig. 2).

MLCK, AQP9 and claudin-1 expression levels in terminal ileum tissues obtained from each group as determined by IHC and western blotting

IHC staining was used to determine MLCK protein expression levels, and the results demonstrated that in the sections of ileum obtained from NC rats, slight positive brown staining revealing MLCK protein expression in the cytoplasm was observed; however, positive staining in the mucosa of terminal ileum tissues obtained from acute liver injury rats at 24, 48 and 72 h time intervals was revealed to be significantly increased in a time-dependent manner (P<0.05; Fig. 3). The greatest protein expression levels of MLCK were demonstrated in the model 72 h group (Fig. 3). The results of western blotting revealed that MLCK protein expression levels were significantly increased compared with the NC group in a time-dependent manner (Fig. 4).

Western blotting was also used to investigate AQP9 and claudin-1 protein expression levels in terminal ileum tissues obtained from all rats. The results revealed that both AQP9 and claudin-1 expression levels were significantly decreased in the terminal ileum of model groups compared with the NC group in a time-dependent manner (P<0.05; Fig. 4).

Concentrations of serum cytokines in NC rats and acute liver injury model rats

Levels of serum TNF-α, IL-6 and IL-10 in each group were determined using ELISA. The results demonstrated that levels of serum TNF-α, IL-6 and IL-10 were significantly increased in the 24 h model group compared with the NC group (P<0.05; Table II). The serum levels of TNF-α, IL-6 and IL-10 were further increased in the 48 h model group. However, in the 72 h model group, levels of TNF-a and IL-6 were suppressed compared with the 48 h group; whereas levels of IL-10 continued to increase in a time-dependent manner (Table II).

Table II.

Concentrations of TNF-α, IL-6 and IL-10 in acute liver injury model rats at three time intervals and normal control rats.

Table II.

Concentrations of TNF-α, IL-6 and IL-10 in acute liver injury model rats at three time intervals and normal control rats.

TNF-α (pg/ml)IL-6 (pg/ml)IL-10 (pg/ml)
NC8.20±3.125.12±1.127.12±2.15
M-24 h 29.20±3.54a 21.60±3.59a 18.69±4.56a
M-48 h 53.40±5.21a 46.52±3.26a 25.78±5.89a
M-72 h 30.60±3.58a 36.89±4.69a 34.65±5.68a

a P<0.05 vs. the NC group. (x±s; n=5). NC, normal control; M, model group; IL, interleukin; TNF-α, tumor necrosis factor-α.

Discussion

Liver diseases have previously been reported to be associated with gastrointestinal function (20). When liver function is severely impaired, it is frequently accompanied by endotoxemia; meanwhile in intestinal barrier function disorders, a large number of intestinal bacteria translocate from the intestinal lumen causing infection, and increasing the production of endotoxins (21). In addition, the intestinal canal represents a bacterial repository, and the largest gram-negative bacterial endotoxin pool (22,23). Therefore, it is very important to maintain intestinal barrier function, limit bacterial translocation and reduce endotoxemia in the treatment of liver disease (23,24).

Intestinal mucosal barrier function is essential for the working of the intestine (25). The normal intestinal mucosal barrier is composed of mechanical, chemical, immune and biological barriers, of which the intestinal mechanical barrier is the most important, and is predominantly composed of intestinal epithelial cells and TJs between the epithelial cells. The mechanical barrier, which physically separates the lumen and the internal milieu, facilitates vectorial transport of nutrients ions, and other substances (26). In addition, there is communication between epithelial cells and the immune system (27). Therefore, the mucosal barrier exhibits physical, biochemical and immune features (25). However, numerous inflammatory diseases may induce intestinal mucosal barrier dysfunction, including fulminant hepatitis (28), chronic obstructive pulmonary disease, uremia, severe acute pancreatitis and peritoneal air exposure (2931). A number of traditional Chinese medicines have been demonstrated to improve intestinal barrier function via inhibition of the nuclear factor-κB-mediated signaling pathway or antioxidative action, inhibiting the production of inflammatory cytokines and upregulation of zona occludens protein 1 mRNA and protein expression levels (29,3234). The involvement of inflammatory cells and inflammatory factors, as well as the immune response, results in damage to the intestinal epithelial barrier caused by liver injury, and our model displays these pathophysiological changes.

The most important element of the intestinal barrier is TJs, which are composed of both cytosolic and integral membrane proteins. TJs represent the main component of the intestinal mucosal mechanical barrier structure and have an important role in maintaining the integrity and permeability of the intestinal mucosa (1,2). Claudin-1 is an important structural protein within TJs (5,35). In liver injury, the permeability of TJs between intestinal epithelia is increased and the distribution of the TJ proteins are markedly altered on the intestinal mucosal surface, as well as in membrane microdomains (36).

TNF-α is an important regulator of intestinal inflammation that induces an increase in intestinal permeability via extracellular signal-regulated kinase 1/2-dependent activation of ETS transcription factor (Elk-1), which subsequently activates the MLCK gene in the nucleus by binding to the promoter region of MLCK (37,38). However, restoration of impaired mucosal barrier function may be achieved via downregulation of MLCK expression (7,8). The results of the present study demonstrated that levels of serum TNF-α in acute liver injury rats increased in a time-dependent manner. All the aforementioned results suggested that the model of acute liver injury-induced impaired mucosal barrier was successfully established.

Water homeostasis is important for neural signal transduction in the nervous system and the function of the intestinal epithelial barrier (4). AQPs were first observed in the nervous system (39). Following this, AQPs were revealed to be widely distributed in the liver, duodenum, jejunum, ileum and colon. AQP9 is a transmembrane protein composed of a single polypeptide transmembrane peptide 6 (40). Both rat and human AQP9 are abundantly expressed in the liver, whereas in contrast to rat AQP9 (41), human AQP9 is also expressed in peripheral leukocytes and in tissues that accumulate leukocytes, including the lung, spleen and bone marrow (10,1114). The promoter region of AQP9 contains putative tonicity and glucocorticoid-responsive elements, suggesting that AQP9 may be regulated by osmolality and catabolism (42), involving osmoregulation of small molecules (43). This mechanism is important to the function of intestinal epithelial barrier (44).

To the best of our knowledge, the present study is the first to investigate the expression and function of AQP9 in the ileum mucosa, and the results demonstrated that expression levels of AQP9 in damaged ileal mucosa were decreased compared with the NC group. Furthermore, the results revealed that claudin-1 expression levels in damaged ileum mucosa were also decreased compared with the NC group; however, MLCK expression levels were increased. These results suggested that AQP9 may have various associations with ileal mucosal damage.

However, the results of the present study have predominantly focused on the association between AQP9 expression levels and the expression of two important makers of the intestinal epithelium; however, the specific molecular mechanism has not been determined. In addition, the present study only investigated the ileum mucosa; the situation of the rest of the small intestine remains unclear.

The results of the present study revealed that AQP9 in the intestinal epithelium has an important role in the development of acute liver injury-induced intestinal epithelium damage.

Acknowledgements

Not applicable.

Funding

The present study was financially supported by the Jiangxi Provincial Health Department (grant nos. 20155100 and 20167202).

Availability of data and materials

The datasets used during the present study are available from the corresponding author upon reasonable request.

Authors' contributions

TX and NC conceived and designed the study. TX, SG, JW, JX, LY and XW performed the experiments. TX and NC wrote the manuscript. All authors read and approved the manuscript.

Ethics approval and consent to participate

All animal experiments were approved by the Animal Ethics Association of the First Affiliated Hospital of Nanchang University.

Patient consent for publication

Not applicable.

Competing interests

The authors state that they have no competing interests.

References

1 

Suzuki T: Regulation of intestinal epithelial permeability by tight junctions. Cell Mol Life Sci. 70:631–659. 2013. View Article : Google Scholar : PubMed/NCBI

2 

Dokladny K, Zuhl MN and Moseley PL: Intestinal epithelial barrier function and tight junction proteins with heat and exercise. J Appl Physiol (1985). 120:692–701. 2016. View Article : Google Scholar : PubMed/NCBI

3 

Muto S: Physiological roles of claudins in kidney tubule paracellular transport. Am J Physiol Renal Physiol. 312:F9–F24. 2017. View Article : Google Scholar : PubMed/NCBI

4 

Khan N and Asif AR: Transcriptional regulators of claudins in epithelial tight junctions. Mediators Inflamm. 2015:2198432015. View Article : Google Scholar : PubMed/NCBI

5 

Gan H, Wang G, Hao Q, Wang QJ and Tang H: Protein kinase D promotes airway epithelial barrier dysfunction and permeability through down-regulation of claudin-1. J Biol Chem. 288:37343–37354. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Ohta A, Yang SS, Rai T, Chiga M, Sasaki S and Uchida S: Overexpression of human WNK1 increases paracellular chloride permeability and phosphorylation of claudin-4 in MDCKII cells. Biochem Biophys Res Commun. 349:804–808. 2006. View Article : Google Scholar : PubMed/NCBI

7 

Du J, Chen Y, Shi Y, Liu T, Cao Y, Tang Y, Ge X, Nie H, Zheng C and Li YC: 1,25-Dihydroxyvitamin D protects intestinal epithelial barrier by regulating the myosin light chain kinase signaling pathway. Inflamm Bowel Dis. 21:2495–2506. 2015. View Article : Google Scholar : PubMed/NCBI

8 

Xiong Y, Wang J, Chu H, Chen D and Guo H: Salvianolic acid B restored impaired barrier function via downregulation of MLCK by microRNA-1 in rat colitis model. Front Pharmacol. 7:1342016. View Article : Google Scholar : PubMed/NCBI

9 

Takata K, Matsuzaki T and Tajika Y: Aquaporins: Water channel proteins of the cell membrane. Prog Histochem Cytochem. 39:1–83. 2004. View Article : Google Scholar : PubMed/NCBI

10 

Carbrey JM, Gorelick-Feldman DA, Kozono D, Praetorius J, Nielsen S and Agre P: Aquaglyceroporin AQP9: Solute permeation and metabolic control of expression in liver. Proc Natl Acad Sci U S A. 100:2945–2950. 2003. View Article : Google Scholar : PubMed/NCBI

11 

Lindskog C, Asplund A, Catrina A, Nielsen S and Rutzler M: A systematic characterization of aquaporin-9 expression in human normal and pathological tissues. J Histochem Cytochem. 64:287–300. 2016. View Article : Google Scholar : PubMed/NCBI

12 

Rojek AM, Skowronski MT, Fuchtbauer EM, Füchtbauer AC, Fenton RA, Agre P, Frøkiaer J and Nielsen S: Defective glycerol metabolism in aquaporin 9 (AQP9) knockout mice. Proc Natl Acad Sci U S A. 104:3609–3614. 2007. View Article : Google Scholar : PubMed/NCBI

13 

Spegel P, Chawade A, Nielsen S, Kjellbom P and Rutzler M: Deletion of glycerol channel aquaporin-9 (Aqp9) impairs long-term blood glucose control in C57BL/6 leptin receptor-deficient (db/db) obese mice. Physiol Rep. 3:e125382015. View Article : Google Scholar : PubMed/NCBI

14 

Okada S, Misaka T, Matsumoto I, Watanabe H and Abe K: Aquaporin-9 is expressed in a mucus-secreting goblet cell subset in the small intestine. FEBS Lett. 540:157–162. 2003. View Article : Google Scholar : PubMed/NCBI

15 

Matsuzaki T, Tajika Y, Ablimit A, Aoki T, Hagiwara H and Takata K: Aquaporins in the digestive system. Med Electron Microsc. 37:71–80. 2004. View Article : Google Scholar : PubMed/NCBI

16 

Liu W, Hou S, Yan J, Zhang H, Ji Y and Wu X: Quantification of proteins using enhanced etching of Ag coated Au nanorods by the Cu(2+)/bicinchoninic acid pair with improved sensitivity. Nanoscale. 8:780–784. 2016. View Article : Google Scholar : PubMed/NCBI

17 

Rudler M, Mouri S, Charlotte F, Lebray P, Capocci R, Benosman H, Poynard T and Thabut D: Prognosis of treated severe alcoholic hepatitis in patients with gastrointestinal bleeding. J Hepatol. 62:816–821. 2015. View Article : Google Scholar : PubMed/NCBI

18 

Konno R, Yamakawa H, Utsunomiya H, Ito K, Sato S and Yajima A: Expression of survivin and Bcl-2 in the normal human endometrium. Mol Hum Reprod. 6:529–534. 2000. View Article : Google Scholar : PubMed/NCBI

19 

Zhang C, Li Y, Zhang XY, Liu L, Tong HZ, Han TL, Li WD, Jin XL, Yin NB, Song T, et al: Therapeutic potential of human minor salivary gland epithelial progenitor cells in liver regeneration. Sci Rep. 7:127072017. View Article : Google Scholar : PubMed/NCBI

20 

Elamin E, Masclee A, Troost F, Pieters HJ, Keszthelyi D, Aleksa K, Dekker J and Jonkers D: Ethanol impairs intestinal barrier function in humans through mitogen activated protein kinase signaling: A combined in vivo and in vitro approach. PloS One. 9:e1074212014. View Article : Google Scholar : PubMed/NCBI

21 

Armand-Lefevre L, Angebault C, Barbier F, Hamelet E, Defrance G, Ruppé E, Bronchard R, Lepeule R, Lucet JC, El Mniai A, et al: Emergence of imipenem-resistant gram-negative bacilli in intestinal flora of intensive care patients. Antimicrob Agents Chemother. 57:1488–1495. 2013. View Article : Google Scholar : PubMed/NCBI

22 

Resino E, San-Juan R and Aguado JM: Selective intestinal decontamination for the prevention of early bacterial infections after liver transplantation. World J Gastroenterol. 22:5950–5957. 2016. View Article : Google Scholar : PubMed/NCBI

23 

Baranova IN, Souza AC, Bocharov AV, Vishnyakova TG, Hu X, Vaisman BL, Amar MJ, Chen Z, Kost Y, Remaley AT, et al: Human SR-BI and SR-BII potentiate lipopolysaccharide-induced inflammation and acute liver and kidney injury in mice. J Immunol. 196:3135–3147. 2016. View Article : Google Scholar : PubMed/NCBI

24 

de Medina Sanchez F, Romero-Calvo I, Mascaraque C and Martinez-Augustin O: Intestinal inflammation and mucosal barrier function. Inflamm Bowel Dis. 20:2394–2404. 2014. View Article : Google Scholar : PubMed/NCBI

25 

Pelaseyed T, Bergstrom JH, Gustafsson JK, Ermund A, Birchenough GM, Schütte A, van der Post S, Svensson F, Rodríguez-Piñeiro AM, Nyström EE, et al: The mucus and mucins of the goblet cells and enterocytes provide the first defense line of the gastrointestinal tract and interact with the immune system. Immunol Rev. 260:8–20. 2014. View Article : Google Scholar : PubMed/NCBI

26 

Turner JR: Intestinal mucosal barrier function in health and disease. Nat Rev Immunol. 9:799–809. 2009. View Article : Google Scholar : PubMed/NCBI

27 

Wang X, Yan S, Xu D, Li J, Xie Y, Hou J, Jiang R, Zhang C and Sun B: Aggravated liver injury but attenuated inflammation in PTPRO-deficient mice following LPS/D-GaIN induced fulminant hepatitis. Cell Physiol Biochem. 37:214–224. 2015. View Article : Google Scholar : PubMed/NCBI

28 

Yu C, Tan S, Zhou C, Zhu C, Kang X, Liu S, Zhao S, Fan S, Yu Z, Peng A and Wang Z: Berberine reduces uremia-associated intestinal mucosal barrier damage. Biol Pharm Bull. 39:1787–1792. 2016. View Article : Google Scholar : PubMed/NCBI

29 

Li HC, Fan XJ, Chen YF, Tu JM, Pan LY, Chen T, Yin PH, Peng W and Feng DX: Early prediction of intestinal mucosal barrier function impairment by elevated serum procalcitonin in rats with severe acute pancreatitis. Pancreatology. 16:211–217. 2016. View Article : Google Scholar : PubMed/NCBI

30 

Tan SJ, Yu C, Yu Z, Lin ZL, Wu GH, Yu WK, Li JS and Li N: High-fat enteral nutrition reduces intestinal mucosal barrier damage after peritoneal air exposure. J Surg Res. 202:77–86. 2016. View Article : Google Scholar : PubMed/NCBI

31 

Wen JB, Zhu FQ, Chen WG, Jiang LP, Chen J, Hu ZP, Huang YJ, Zhou ZW, Wang GL, Lin H and Zhou SF: Oxymatrine improves intestinal epithelial barrier function involving NF-κB-mediated signaling pathway in CCl4-induced cirrhotic rats. PLoS One. 9:e1060822014. View Article : Google Scholar : PubMed/NCBI

32 

Chen J, Zhang R, Wang J, Yu P, Liu Q, Zeng D, Song H and Kuang Z: Protective effects of baicalin on LPS-induced injury in intestinal epithelial cells and intercellular tight junctions. Can J Physiol Pharmacol. 93:233–237. 2015. View Article : Google Scholar : PubMed/NCBI

33 

Zong X, Hu W, Song D, Li Z, Du H, Lu Z and Wang Y: Porcine lactoferrin-derived peptide LFP-20 protects intestinal barrier by maintaining tight junction complex and modulating inflammatory response. Biochem Pharmacol. 104:74–82. 2016. View Article : Google Scholar : PubMed/NCBI

34 

Saeedi BJ, Kao DJ, Kitzenberg DA, Dobrinskikh E, Schwisow KD, Masterson JC, Kendrick AA, Kelly CJ, Bayless AJ, Kominsky DJ, et al: HIF-dependent regulation of claudin-1 is central to intestinal epithelial tight junction integrity. Mol Biol Cell. 26:2252–2262. 2015. View Article : Google Scholar : PubMed/NCBI

35 

Al-Sadi R, Guo S, Ye D, Rawat M and Ma TY: TNF-α modulation of intestinal tight junction permeability is mediated by NIK/IKK-α axis activation of the canonical NF-κB pathway. Am J Pathol. 186:1151–1165. 2016. View Article : Google Scholar : PubMed/NCBI

36 

Liu R, Li X, Huang Z, Zhao D, Ganesh BS, Lai G, Pandak WM, Hylemon PB, Bajaj JS, Sanyal AJ and Zhou H: C/EBP homologous protein-induced loss of intestinal epithelial stemness contributes to bile duct ligation-induced cholestatic liver injury in mice. Hepatology. 67:1441–1457. 2018. View Article : Google Scholar : PubMed/NCBI

37 

Al-Sadi R, Guo S, Ye D and Ma TY: TNF-α modulation of intestinal epithelial tight junction barrier is regulated by ERK1/2 activation of Elk-1. Am J Pathol. 183:1871–1884. 2013. View Article : Google Scholar : PubMed/NCBI

38 

Guérin CF, Regli L and Badaut J: Roles of aquaporins in the brain. Med Sci (Paris). 21:747–752. 2005.(In French). View Article : Google Scholar : PubMed/NCBI

39 

Dibas A, Yang MH, Bobich J and Yorio T: Stress-induced changes in neuronal Aquaporin-9 (AQP9) in a retinal ganglion cell-line. Pharmacol Res. 55:378–384. 2007. View Article : Google Scholar : PubMed/NCBI

40 

Chen XF, Li CF, Lu L and Mei ZC: Expression and clinical significance of aquaglyceroporins in human hepatocellular carcinoma. Mol Med Rep. 13:5283–5289. 2016. View Article : Google Scholar : PubMed/NCBI

41 

Liu Z, Carbrey JM, Agre P and Rosen BP: Arsenic trioxide uptake by human and rat aquaglyceroporins. Biochem Biophys Res Commun. 316:1178–1185. 2004. View Article : Google Scholar : PubMed/NCBI

42 

Tsukaguehi H, Weremowiez S, Morton CC and Hediger MA: Funetional and molecular characterization of the human neutral solute channel aquaporin-9. Am J Physiol. 277:F685–F696. 1999.PubMed/NCBI

43 

Yang M, Gao F, Liu H, Yu WH, Zhuo F, Qiu GP, Ran JH and Sun SQ: Hyperosmotic induction of aquaporin expression in rat astrocytes through a different MAPK pathway. J Cell Biochem. 114:111–119. 2013. View Article : Google Scholar : PubMed/NCBI

44 

Lei Q, Qiang F, Chao D, Di W, Guoqian Z, Bo Y and Lina Y: Amelioration of hypoxia and LPS-induced intestinal epithelial barrier dysfunction by emodin through the suppression of the NF-kappaB and HIF-1alpha signaling pathways. Int J Mol Med. 34:1629–1639. 2014. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

December-2018
Volume 18 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Xiang T, Ge S, Wen J, Xie J, Yang L, Wu X and Cheng N: The possible association between AQP9 in the intestinal epithelium and acute liver injury‑induced intestinal epithelium damage. Mol Med Rep 18: 4987-4993, 2018
APA
Xiang, T., Ge, S., Wen, J., Xie, J., Yang, L., Wu, X., & Cheng, N. (2018). The possible association between AQP9 in the intestinal epithelium and acute liver injury‑induced intestinal epithelium damage. Molecular Medicine Reports, 18, 4987-4993. https://doi.org/10.3892/mmr.2018.9542
MLA
Xiang, T., Ge, S., Wen, J., Xie, J., Yang, L., Wu, X., Cheng, N."The possible association between AQP9 in the intestinal epithelium and acute liver injury‑induced intestinal epithelium damage". Molecular Medicine Reports 18.6 (2018): 4987-4993.
Chicago
Xiang, T., Ge, S., Wen, J., Xie, J., Yang, L., Wu, X., Cheng, N."The possible association between AQP9 in the intestinal epithelium and acute liver injury‑induced intestinal epithelium damage". Molecular Medicine Reports 18, no. 6 (2018): 4987-4993. https://doi.org/10.3892/mmr.2018.9542