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Intestinal flora imbalance promotes alcohol‑induced liver fibrosis by the TGFβ/smad signaling pathway in mice

  • Authors:
    • Dong Zhang
    • Xiuxian Hao
    • Lili Xu
    • Jing Cui
    • Li Xue
    • Zibin Tian
  • View Affiliations / Copyright

    Affiliations: Medical College, Qingdao University, Qingdao, Shandong 266042, P.R. China, Department of Endocrinology, Qingdao Center Hospital, Qingdao, Shandong 266042, P.R. China, Department of Endocrinology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China, Department of Emergency, The Third People's Hospital of Qingdao, Qingdao, Shandong 266041, P.R. China, Department of Gastroenterology, Qingdao Center Hospital, Qingdao, Shandong 266042, P.R. China, Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4511-4516
    |
    Published online on: August 17, 2017
       https://doi.org/10.3892/ol.2017.6762
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Abstract

Intestinal flora performs a crucial role in human health and its imbalance may cause numerous pathological changes. The liver can also affect the intestinal function through bile secretion via the enterohepatic cycle. The pathophysiological association between the gut and the liver is described as the gut‑liver axis. The present study investigated the role of intestinal flora in alcohol‑induced liver fibrosis. A total of 36 C57 mice were randomly and equally divided into 3 different dietary regimes: Group I (alcohol injury; received alcohol); group II (alcohol injury with flora imbalance; received alcohol plus lincomycin hydrochloride) and group III (alcohol injury with corrected flora imbalance; received alcohol, lincomycin hydrochloride and extra probiotics). The present study then investigated several indicators of liver damage. Alkaline phosphatase (ALP) levels, aspartate aminotransferase (AST) levels and alanine aminotransferase (ALT) levels in mice serum were studied. Masson staining and Annexin V‑fluorescein isothiocyanate/propidium iodide double staining was also performed, and the expression of mothers against decapentaplegic homolog (smad) 3 and smad4 proteins in hepatic stellate cells (HSCs) of the mice was examined using western blot analysis. The levels of serum ALP, AST and ALT were the highest in group II mice, and all 3 levels decreased in group III mice compared with those from group II. The degree of liver fibrosis was aggravated in group II mice compared with group I mice. The apoptosis of HSCs was significantly inhibited in group II mice, but was increased in group III mice. The HSCs in group II mice exhibited higher expression of smad3 and smad4, whilst group III mice (with corrected intestinal flora imbalance) exhibited downregulated expression of smad3 and smad4. The present data indicates that the intestinal flora perform a significant role in maintaining liver homeostasis. Furthermore, an imbalance of intestinal flora can exacerbate alcohol‑induced liver fibrosis in mice through the transforming growth factor β/SMA/MAD homology signaling pathway, which subsequently leads to more serious liver damage.
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1 

Blachier M, Leleu H, Peck-Radosavljevic M, Valla DC and Roudot-Thoraval F: The burden of liver disease in Europe: A review of available epidemiological data. J Hepatol. 58:593–608. 2013. View Article : Google Scholar : PubMed/NCBI

2 

Bataller R and Brenner DA: Liver fibrosis. J Clin Invest. 115:209–218. 2005. View Article : Google Scholar : PubMed/NCBI

3 

Szabo G and Bala S: Alcoholic liver disease and the gut-liver axis. World J Gastroenterol. 16:1321–1329. 2010. View Article : Google Scholar : PubMed/NCBI

4 

Wu ZW, Ling ZX, Lu HF, Zuo J, Sheng JF, Zheng SS and Li LJ: Changes of gut bacteria and immune parameters in liver transplant recipients. Hepatobiliary Pancreat Dis Int. 11:40–50. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Yang Y, Kim B, Park YK, Koo SI and Lee JY: Astaxanthin prevents TGFβ1-induced pro-fibrogenic gene expression by inhibiting Smad3 activation in hepatic stellate cells. Biochim Biophys Acta. 1850:178–185. 2015. View Article : Google Scholar : PubMed/NCBI

6 

Liu Q, Duan ZP, Ha DK, Bengmark S, Kurtovic J and Riordan SM: Synbiotic modulation of gut flora: Effect on minimal hepatic encephalopathy in patients with cirrhosis. Hepatology. 39:1441–1449. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Lata J, Novotný I, Príbramská V, Juránková J, Fric P, Kroupa R and Stibůrek O: The effect of probiotics on gut flora, level of endotoxin and child-pugh score in cirrhotic patients: Results of a double-blind randomized study. Eur J Gastroenterol Hepatol. 19:1111–1113. 2007. View Article : Google Scholar : PubMed/NCBI

8 

Shukla S, Shukla A, Mehboob S and Guha S: Meta-analysis: The effects of gut flora modulation using prebiotics, probiotics and synbiotics on minimal hepatic encephalopathy. Aliment Pharmacol Ther. 33:662–671. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Bauer TM, Schwacha H, Steinbrückner B, Brinkmann FE, Ditzen AK, Aponte JJ, Pelz K, Berger D, Kist M and Blum HE: Small intestinal bacterial overgrowth in human cirrhosis is associated with systemic endotoxemia. Am J Gastroenterol. 97:2364–2370. 2002. View Article : Google Scholar : PubMed/NCBI

10 

Maddrey WC: Alcohol-induced liver disease. Clin Liver Dis. 4:115–131, vii. 2000. View Article : Google Scholar : PubMed/NCBI

11 

Yan G, Li B, Xin X, Xu M, Ji G and Yu H: MicroRNA-34a promotes hepatic stellate cell activation via targeting ACSL1. Med Sci Monit. 21:3008–3015. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Jarzembowski T, Daca A, Bryl E, Wiśniewska K, Gołębiewska J, Dębska-Ślizień A, Rutkowski B and Witkowski J: Increased pheromone cCF10 expression in Enterococcus faecalis biofilm formed by isolates from renal transplant patients. Curr Microbiol. 65:656–659. 2012. View Article : Google Scholar : PubMed/NCBI

13 

Li L, Wu Z, Ma W, Yu Y and Chen Y: Changes in intestinal microflora in patients with chronic severe hepatitis. Chin Med J (Engl). 114:869–872. 2001.PubMed/NCBI

14 

Schreiber S, Rosenstiel P, Albrecht M, Hampe J and Krawczak M: Genetics of Crohn disease, an archetypal inflammatory barrier disease. Nat Rev Genet. 6:376–388. 2005. View Article : Google Scholar : PubMed/NCBI

15 

Housset C and Guéchot J: Hepatic fibrosis: Physiopathology and biological diagnosis. Pathol Biol (Paris). 47:886–894. 1999.(In French). PubMed/NCBI

16 

Liao SL, Kao TK, Chen WY, Lin YS, Chen SY, Raung SL, Wu CW, Lu HC and Chen CJ: Tetramethylpyrazine reduces ischemic brain injury in rats. Neurosci Lett. 372:40–45. 2004. View Article : Google Scholar : PubMed/NCBI

17 

Nozaki Y, Fujita K, Wada K, Yoneda M, Kessoku T, Shinohara Y, Imajo K, Ogawa Y, Nakamuta M, Saito S, et al: Deficiency of iNOS-derived NO accelerates lipid accumulation-independent liver fibrosis in non-alcoholic steatohepatitis mouse model. BMC Gastroenterol. 15:422015. View Article : Google Scholar : PubMed/NCBI

18 

Reyes-Gordillo K, Shah R, Arellanes-Robledo J, Hernández-Nazara Z, Rincón-Sánchez AR, Inagaki Y, Rojkind M and Lakshman MR: Mechanisms of action of acetaldehyde in the up-regulation of the human α2(I) collagen gene in hepatic stellate cells: Key roles of Ski, SMAD3, SMAD4, and SMAD7. Am J Pathol. 184:1458–1467. 2014. View Article : Google Scholar : PubMed/NCBI

19 

O'Reilly S, Ciechomska M, Cant R and van Laar JM: Interleukin-6 (IL-6) trans signaling drives a STAT3-dependent pathway that leads to hyperactive transforming growth factor-β (TGF-β) signaling promoting SMAD3 activation and fibrosis via Gremlin protein. J Biol Chem. 289:9952–9960. 2014. View Article : Google Scholar : PubMed/NCBI

20 

Sun YB, Qu X, Li X, Nikolic-Paterson DJ and Li J: Endothelial dysfunction exacerbates renal interstitial fibrosis through enhancing fibroblast Smad3 linker phosphorylation in the mouse obstructed kidney. PLoS One. 8:e840632013. View Article : Google Scholar : PubMed/NCBI

21 

Huang XZ, Wen D, Zhang M, Xie Q, Ma L, Guan Y, Ren Y, Chen J and Hao CM: Sirt1 activation ameliorates renal fibrosis by inhibiting the TGF-β/Smad3 pathway. J Cell Biochem. 115:996–1005. 2014. View Article : Google Scholar : PubMed/NCBI

22 

Schwartze JT, Becker S, Sakkas E, Wujak ŁA, Niess G, Usemann J, Reichenberger F, Herold S, Vadász I, Mayer K, et al: Glucocorticoids recruit Tgfbr3 and Smad1 to shift transforming growth factor-β signaling from the Tgfbr1/Smad2/3 axis to the Acvrl1/Smad1 axis in lung fibroblasts. J Biol Chem. 289:3262–3275. 2014. View Article : Google Scholar : PubMed/NCBI

23 

Zhu JN, Chen R, Fu YH, Lin QX, Huang S, Guo LL, Zhang MZ, Deng CY, Zou X, Zhong SL, et al: Smad3 inactivation and MiR-29b upregulation mediate the effect of carvedilol on attenuating the acute myocardium infarction-induced myocardial fibrosis in rat. PLoS One. 8:e755572013. View Article : Google Scholar : PubMed/NCBI

24 

Lv KY, Zhong QS, Liu XF, Zhu SH, Xiao SC, Wang GY, Ma B and Xia ZF: Deficiency of Smad3 results in enhanced inducible nitric oxide synthase-mediated hypotension in lipopolysaccharide-induced endotoxemia. J Surg Res. 187:640–645. 2014. View Article : Google Scholar : PubMed/NCBI

25 

Ji F, Fu SJ, Shen SL, Zhang LJ, Cao QH, Li SQ, Peng BG, Liang LJ and Hua YP: The prognostic value of combined TGF-β1 and ELF in hepatocellular carcinoma. BMC Cancer. 15:1162015. View Article : Google Scholar : PubMed/NCBI

26 

Kamato D, Burch ML, Piva TJ, Rezaei HB, Rostam MA, Xu S, Zheng W, Little PJ and Osman N: Transforming growth factor-β signalling: Role and consequences of Smad linker region phosphorylation. Cell Signal. 25:2017–2024. 2013. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Zhang D, Hao X, Xu L, Cui J, Xue L and Tian Z: Intestinal flora imbalance promotes alcohol‑induced liver fibrosis by the TGFβ/smad signaling pathway in mice. Oncol Lett 14: 4511-4516, 2017.
APA
Zhang, D., Hao, X., Xu, L., Cui, J., Xue, L., & Tian, Z. (2017). Intestinal flora imbalance promotes alcohol‑induced liver fibrosis by the TGFβ/smad signaling pathway in mice. Oncology Letters, 14, 4511-4516. https://doi.org/10.3892/ol.2017.6762
MLA
Zhang, D., Hao, X., Xu, L., Cui, J., Xue, L., Tian, Z."Intestinal flora imbalance promotes alcohol‑induced liver fibrosis by the TGFβ/smad signaling pathway in mice". Oncology Letters 14.4 (2017): 4511-4516.
Chicago
Zhang, D., Hao, X., Xu, L., Cui, J., Xue, L., Tian, Z."Intestinal flora imbalance promotes alcohol‑induced liver fibrosis by the TGFβ/smad signaling pathway in mice". Oncology Letters 14, no. 4 (2017): 4511-4516. https://doi.org/10.3892/ol.2017.6762
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang D, Hao X, Xu L, Cui J, Xue L and Tian Z: Intestinal flora imbalance promotes alcohol‑induced liver fibrosis by the TGFβ/smad signaling pathway in mice. Oncol Lett 14: 4511-4516, 2017.
APA
Zhang, D., Hao, X., Xu, L., Cui, J., Xue, L., & Tian, Z. (2017). Intestinal flora imbalance promotes alcohol‑induced liver fibrosis by the TGFβ/smad signaling pathway in mice. Oncology Letters, 14, 4511-4516. https://doi.org/10.3892/ol.2017.6762
MLA
Zhang, D., Hao, X., Xu, L., Cui, J., Xue, L., Tian, Z."Intestinal flora imbalance promotes alcohol‑induced liver fibrosis by the TGFβ/smad signaling pathway in mice". Oncology Letters 14.4 (2017): 4511-4516.
Chicago
Zhang, D., Hao, X., Xu, L., Cui, J., Xue, L., Tian, Z."Intestinal flora imbalance promotes alcohol‑induced liver fibrosis by the TGFβ/smad signaling pathway in mice". Oncology Letters 14, no. 4 (2017): 4511-4516. https://doi.org/10.3892/ol.2017.6762
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