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Application of TGF‑β1, TIMP‑1 and TIMP‑2 small interfering RNAs can alleviate CCl4‑induced hepatic fibrosis in rats by rebalancing Th1/Th2 cytokines

  • Authors:
    • Ying Xue
    • Keli Qian
    • Yinchun Sun
    • Lang Xiao
    • Xiaofeng Shi
  • View Affiliations / Copyright

    Affiliations: Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Institute for Virus Hepatitis and Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China
    Copyright: © Xue et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 963
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    Published online on: July 7, 2021
       https://doi.org/10.3892/etm.2021.10395
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Abstract

The present study aimed to investigate the effects of TGF‑β1, tissue inhibitor of metalloproteinase (TIMP)‑1 small interfering (si)RNA and TIMP‑2 siRNA on hepatic fibrosis in rats and explore the T helper (Th)1/Th2 balance. Moreover, IFN‑γ, IL‑4 and IL‑13 are the main cytokines associated with Th1/Th2 responses and have significant influence on the progression of hepatic fibrosis. The expression levels of IFN‑γ, IL‑4 and IL‑13 in rats with hepatic fibrosis that were treated with siRNAs against the aforementioned molecules were measured using various techniques including immunohistochemical staining, western blotting and reverse transcription‑quantitative PCR. The principal outcomes revealed the downregulation of IFN‑γ and the upregulation of IL‑4 and IL‑13 in the model group compared with the normal group. Moreover, the expression of IFN‑γ was significantly increased, while IL‑4 and IL‑13 demonstrated no significant difference in the TGF‑β1 siRNA treatment group compared with the model group. The TIMP‑1 and TIMP‑2 siRNA treatment groups exhibited significantly increased expression levels of IFN‑γ, but lower expression levels of IL‑4 and IL‑13 compared with the model group. These results indicated that TIMP‑1 and TIMP‑2 were improved antifibrotic targets compared with TGF‑β1.
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1 

Campana L and Iredale JP: Regression of liver fibrosis. Semin Liver Dis. 37:1–10. 2017.PubMed/NCBI View Article : Google Scholar

2 

Tsuchida T and Friedman SL: Mechanisms of hepatic stellate cell activation. Nat Rev Gastroenterol Hepatol. 14:397–411. 2017.PubMed/NCBI View Article : Google Scholar

3 

Xing ZZ, Huang LY, Wu CR, You H, Ma H and Jia JD: Activated rat hepatic stellate cells influence Th1/Th2 profile in vitro. World J Gastroenterol. 21:7165–7171. 2015.PubMed/NCBI View Article : Google Scholar

4 

Schumacher JD and Guo GL: Regulation of hepatic stellate cells and fibrogenesis by fibroblast growth factors. Biomed Res Int. 2016(8323747)2016.PubMed/NCBI View Article : Google Scholar

5 

Lang Q, Liu Q, Xu N, Qian KL, Qi JH, Sun YC, Xiao L and Shi XF: The antifibrotic effects of TGF-β1 siRNA on hepatic fibrosis in rats. Biochem Biophys Res Commun. 409:448–453. 2011.PubMed/NCBI View Article : Google Scholar

6 

Cheng X, Zhang M, Xue Y, Sun H, Liu Q and Shi XF: Effect of tissue inhibitor of metalloproteinase-1 and 2 siRNA on the expression of smad2/3/4 protein in hepatic stellate cells. Zhonghua Gan Zang Bing Za Zhi. 28:753–759. 2020.PubMed/NCBI View Article : Google Scholar : (In Chinese).

7 

Qian KL, Xu N, Lang Q, Qi JH, Sun YC, Xiao L, Liu Q and Shi XF: Construction and identification of siRNA eukaryotic expression vectors targeting on TGFβ1, TIMP-1 and TIMP-2 genes in vitro. Zhonghua Gan Zang Bing Za Zhi. 19:291–296. 2011.PubMed/NCBI View Article : Google Scholar : (In Chinese).

8 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar

9 

Rockey DC, Bell PD and Hill JA: Fibrosis-a common pathway to organ injury and failure. N Engl J Med. 372:1138–1149. 2015.PubMed/NCBI View Article : Google Scholar

10 

Weiskirchen R, Weiskirchen S and Tacke F: Organ and tissue fibrosis: Molecular signals, cellular mechanisms and translational implications. Mol Aspects Med. 65:2–15. 2019.PubMed/NCBI View Article : Google Scholar

11 

Liu C, Zhang YS, Chen F, Wu XY, Zhang BB, Wu ZD and Lei JX: Immunopathology in schistosomiasis is regulated by TLR2, 4- and IFN-γ-activated MSC through modulating Th1/Th2 responses. Stem Cell Res Ther. 11(217)2020.PubMed/NCBI View Article : Google Scholar

12 

Euler T, Valesky EM, Meissner M, Hrgovic I, Kaufmann R, Kippenberger S and Zöller NN: Normal and keloid fibroblasts are differentially influenced by IFN-γ and triamcinolone as well as by their combination. Wound Repair Regen. 27:450–461. 2019.PubMed/NCBI View Article : Google Scholar

13 

Kannan AK, Sahu N, Mohanan S, Mohinta S and August A: IL-2-inducible T-cell kinase modulates TH2-mediated allergic airway inflammation by suppressing IFN-γ in naive CD4+ T cells. J Allergy Clin Immunol. 132:811–820.e1-e5. 2013.PubMed/NCBI View Article : Google Scholar

14 

Oh JE, Shim KY, Lee JI, Choi SI, Baik SK and Eom YW: 1-Methyl-L-tryptophan promotes the apoptosis of hepatic stellate cells arrested by interferon-γ by increasing the expression of IFN-γRβ, IRF-1 and FAS. Int J Mol Med. 40:576–582. 2017.PubMed/NCBI View Article : Google Scholar

15 

Li F, Li QH, Wang JY, Zhan CY, Xie C and Lu WY: Effects of interferon-gamma liposomes targeted to platelet-derived growth factor receptor-beta on hepatic fibrosis in rats. J Control Release. 159:261–270. 2012.PubMed/NCBI View Article : Google Scholar

16 

Cortes-Selva D, Ready A, Gibbs L, Rajwa B and Fairfax KC: IL-4 promotes stromal cell expansion and is critical for development of a type-2, but not a type 1 immune response. Eur J Immunol. 49:428–442. 2019.PubMed/NCBI View Article : Google Scholar

17 

Atsukawa K, Saito H, Tsukada N, Akiba Y, Toda K, Kumagai N, Ohishi T, Kamegaya Y and Ishii H: Th1 and Th2 cytokines differentially regulate the transformation of Kupffer cells into multinucleated giant cells but similarly enhance the Kupffer cell-induced hepatic stellate cell proliferation. Hepatol Res. 20:193–206. 2001.PubMed/NCBI View Article : Google Scholar

18 

Bergeron C, Pagé N, Barbeau B and Chakir J: Interleukin-4 promotes airway remodeling in asthma: Regulation of procollagen I (alpha1) gene by interleukin-4. Chest. 123 (Suppl 3)(424S)2003.PubMed/NCBI View Article : Google Scholar

19 

Weng SY, Wang X, Vijayan S, Tang Y, Kim YO, Padberg K, Regen T, Molokanova O, Chen T, Bopp T, et al: IL-4 Receptor alpha signaling through macrophages differentially regulates liver fibrosis progression and reversal. EBioMedicine. 29:92–103. 2018.PubMed/NCBI View Article : Google Scholar

20 

Coutinho HM, Acosta LP, Wu HW, McGarvey ST, Su L, Langdon GC, Jiz MA, Jarilla B, Olveda RM, Friedman JF and Kurtis JD: Th2 cytokines are associated with persistent hepatic fibrosis in human Schistosoma japonicum infection. J Infect Dis. 195:288–295. 2007.PubMed/NCBI View Article : Google Scholar

21 

Wynn TA: Fibrotic disease and the T(H)1/T(H)2 paradigm. Nat Rev Immunol. 4:583–594. 2004.PubMed/NCBI View Article : Google Scholar

22 

Bhogal RK and Bona CA: Regulatory effect of extracellular signal-regulated kinases (ERK) on type I collagen synthesis in human dermal fibroblasts stimulated by IL-4 and IL-13. Int Rev Immunol. 27:472–496. 2008.PubMed/NCBI View Article : Google Scholar

23 

Yan J, Zhang Z, Yang J, Mitch WE and Wang Y: JAK3/STAT6 Stimulates bone marrow-derived fibroblast activation in renal fibrosis. J Am Soc Nephrol. 26:3060–3071. 2015.PubMed/NCBI View Article : Google Scholar

24 

Sugimoto R, Enjoji M, Nakamuta M, Ohta S, Kohjima M, Fukushima M, Kuniyoshi M, Arimura E, Morizono S, Kotoh K and Nawata H: Effect of IL-4 and IL-13 on collagen production in cultured LI90 human hepatic stellate cells. Liver Int. 25:420–428. 2005.PubMed/NCBI View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Xue Y, Qian K, Sun Y, Xiao L and Shi X: Application of TGF‑β1, TIMP‑1 and TIMP‑2 small interfering RNAs can alleviate CCl<sub>4</sub>‑induced hepatic fibrosis in rats by rebalancing Th1/Th2 cytokines. Exp Ther Med 22: 963, 2021.
APA
Xue, Y., Qian, K., Sun, Y., Xiao, L., & Shi, X. (2021). Application of TGF‑β1, TIMP‑1 and TIMP‑2 small interfering RNAs can alleviate CCl<sub>4</sub>‑induced hepatic fibrosis in rats by rebalancing Th1/Th2 cytokines. Experimental and Therapeutic Medicine, 22, 963. https://doi.org/10.3892/etm.2021.10395
MLA
Xue, Y., Qian, K., Sun, Y., Xiao, L., Shi, X."Application of TGF‑β1, TIMP‑1 and TIMP‑2 small interfering RNAs can alleviate CCl<sub>4</sub>‑induced hepatic fibrosis in rats by rebalancing Th1/Th2 cytokines". Experimental and Therapeutic Medicine 22.3 (2021): 963.
Chicago
Xue, Y., Qian, K., Sun, Y., Xiao, L., Shi, X."Application of TGF‑β1, TIMP‑1 and TIMP‑2 small interfering RNAs can alleviate CCl<sub>4</sub>‑induced hepatic fibrosis in rats by rebalancing Th1/Th2 cytokines". Experimental and Therapeutic Medicine 22, no. 3 (2021): 963. https://doi.org/10.3892/etm.2021.10395
Copy and paste a formatted citation
x
Spandidos Publications style
Xue Y, Qian K, Sun Y, Xiao L and Shi X: Application of TGF‑β1, TIMP‑1 and TIMP‑2 small interfering RNAs can alleviate CCl<sub>4</sub>‑induced hepatic fibrosis in rats by rebalancing Th1/Th2 cytokines. Exp Ther Med 22: 963, 2021.
APA
Xue, Y., Qian, K., Sun, Y., Xiao, L., & Shi, X. (2021). Application of TGF‑β1, TIMP‑1 and TIMP‑2 small interfering RNAs can alleviate CCl<sub>4</sub>‑induced hepatic fibrosis in rats by rebalancing Th1/Th2 cytokines. Experimental and Therapeutic Medicine, 22, 963. https://doi.org/10.3892/etm.2021.10395
MLA
Xue, Y., Qian, K., Sun, Y., Xiao, L., Shi, X."Application of TGF‑β1, TIMP‑1 and TIMP‑2 small interfering RNAs can alleviate CCl<sub>4</sub>‑induced hepatic fibrosis in rats by rebalancing Th1/Th2 cytokines". Experimental and Therapeutic Medicine 22.3 (2021): 963.
Chicago
Xue, Y., Qian, K., Sun, Y., Xiao, L., Shi, X."Application of TGF‑β1, TIMP‑1 and TIMP‑2 small interfering RNAs can alleviate CCl<sub>4</sub>‑induced hepatic fibrosis in rats by rebalancing Th1/Th2 cytokines". Experimental and Therapeutic Medicine 22, no. 3 (2021): 963. https://doi.org/10.3892/etm.2021.10395
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