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miR‑203 inhibits the expression of collagen‑related genes and the proliferation of hepatic stellate cells through a SMAD3‑dependent mechanism

  • Authors:
    • Danping Hu
    • Yibing Hu
    • Wangwang Xu
    • Huanhuan Yu
    • Naibin Yang
    • Shunlan Ni
    • Rongquan Fu
  • View Affiliations / Copyright

    Affiliations: Department of Infectious Diseases, The Third Affiliated Hospital of Wenzhou Medical University, Rui'an, Zhejiang 325200, P.R. China, Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
    Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1248-1254
    |
    Published online on: June 6, 2017
       https://doi.org/10.3892/mmr.2017.6702
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Abstract

Activation of hepatic stellate cells (HSCs) is a pivotal event during hepatic fibrogenesis. Activated HSCs are the main source of collagen and other extracellular matrix (ECM) components, and emerging antifibrotic therapies are aimed at preventing ECM synthesis and deposition. MicroRNAs (miRNAs) have been demonstrated to exert regulatory effects on HSC activation and ECM synthesis. In the present study, the HSC‑T6 rat hepatic stellate cell line was transiently transfected with a miRNA (miR)‑203 mimic, which is an artificial miRNA that enhances the function of miR‑203, with a miR‑203 inhibitor or with a scramble miRNA negative control. mRNA and protein expression levels of collagen (COL) 1A1, COL3A1, α‑smooth muscle actin (α‑SMA) and mothers against decapentaplegic homolog 3 (SMAD3) were assessed using reverse transcription‑quantitative polymerase chain reaction and western blot analysis, respectively. The interaction between miR‑203 and the 3'‑untranslated region (UTR) of SMAD3 mRNA was examined using a dual‑luciferase reporter assay. The proliferative capabilities of activated HSCs were measured using an MTT assay. The present results demonstrated that the mRNA and protein expression levels of COL1A1, COL3A1, α‑SMA and SMAD3 were significantly upregulated following transfection of HSC‑T6 cells with the miR‑203 inhibitor. Conversely, COL1A1, COL3A1, α‑SMA, and SMAD3 mRNA and protein expression appeared to be downregulated in rat HSCs transfected with miR‑203 mimics. Notably, the inhibition of miR‑203 expression was revealed to promote HSC proliferation, whereas increased miR‑203 expression suppressed the proliferative capabilities of HSC‑T6 cells. Furthermore, SMAD3 was revealed to be a direct target of miR‑203. The present study suggested that miR‑203 may function to prevent the synthesis and deposition of ECM components, including COL1A1, COL3A1 and α‑SMA, and to inhibit the proliferation of HSCs through a SMAD3‑dependent mechanism. Therefore, it may be hypothesized that miR‑203 has potential as a novel target for the development of alternative therapeutic strategies for the treatment of patients with hepatic fibrosis in clinical practice.
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Copy and paste a formatted citation
Spandidos Publications style
Hu D, Hu Y, Xu W, Yu H, Yang N, Ni S and Fu R: miR‑203 inhibits the expression of collagen‑related genes and the proliferation of hepatic stellate cells through a SMAD3‑dependent mechanism. Mol Med Rep 16: 1248-1254, 2017.
APA
Hu, D., Hu, Y., Xu, W., Yu, H., Yang, N., Ni, S., & Fu, R. (2017). miR‑203 inhibits the expression of collagen‑related genes and the proliferation of hepatic stellate cells through a SMAD3‑dependent mechanism. Molecular Medicine Reports, 16, 1248-1254. https://doi.org/10.3892/mmr.2017.6702
MLA
Hu, D., Hu, Y., Xu, W., Yu, H., Yang, N., Ni, S., Fu, R."miR‑203 inhibits the expression of collagen‑related genes and the proliferation of hepatic stellate cells through a SMAD3‑dependent mechanism". Molecular Medicine Reports 16.2 (2017): 1248-1254.
Chicago
Hu, D., Hu, Y., Xu, W., Yu, H., Yang, N., Ni, S., Fu, R."miR‑203 inhibits the expression of collagen‑related genes and the proliferation of hepatic stellate cells through a SMAD3‑dependent mechanism". Molecular Medicine Reports 16, no. 2 (2017): 1248-1254. https://doi.org/10.3892/mmr.2017.6702
Copy and paste a formatted citation
x
Spandidos Publications style
Hu D, Hu Y, Xu W, Yu H, Yang N, Ni S and Fu R: miR‑203 inhibits the expression of collagen‑related genes and the proliferation of hepatic stellate cells through a SMAD3‑dependent mechanism. Mol Med Rep 16: 1248-1254, 2017.
APA
Hu, D., Hu, Y., Xu, W., Yu, H., Yang, N., Ni, S., & Fu, R. (2017). miR‑203 inhibits the expression of collagen‑related genes and the proliferation of hepatic stellate cells through a SMAD3‑dependent mechanism. Molecular Medicine Reports, 16, 1248-1254. https://doi.org/10.3892/mmr.2017.6702
MLA
Hu, D., Hu, Y., Xu, W., Yu, H., Yang, N., Ni, S., Fu, R."miR‑203 inhibits the expression of collagen‑related genes and the proliferation of hepatic stellate cells through a SMAD3‑dependent mechanism". Molecular Medicine Reports 16.2 (2017): 1248-1254.
Chicago
Hu, D., Hu, Y., Xu, W., Yu, H., Yang, N., Ni, S., Fu, R."miR‑203 inhibits the expression of collagen‑related genes and the proliferation of hepatic stellate cells through a SMAD3‑dependent mechanism". Molecular Medicine Reports 16, no. 2 (2017): 1248-1254. https://doi.org/10.3892/mmr.2017.6702
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