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Article

Hypoxia‑inducible factor 1α and ROCK1 regulate proliferation and collagen synthesis in hepatic stellate cells under hypoxia

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

    Affiliations: Department of Infectious Diseases, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325200, P.R. China
  • Pages: 3997-4003
    |
    Published online on: August 17, 2018
       https://doi.org/10.3892/mmr.2018.9397
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Abstract

Hypoxia serves a critical role in the pathogenesis of liver fibrosis. Hypoxia‑inducible factor 1α (HIF1‑α) is induced when cells are exposed to low O2 concentrations. Recently, it has been suggested that Rho‑associated coiled‑coil‑forming kinase 1 (ROCK1) may be an important HIF1‑α regulator. In the present study, it was analyzed whether crosstalk between HIF1‑α and ROCK1 regulates cell proliferation and collagen synthesis in hepatic stellate cells (HSCs) under hypoxic conditions. For this purpose, a rat hepatic HSC line (HSC‑T6) was cultured under hypoxic or normoxic conditions, and HIF1‑α and ROCK1 expression was measured at different time points. Additionally, HSC‑T6 cells were transfected with HIF1‑α small interfering RNA (siHIF1‑α), and measured protein expression and mRNA transcript levels of α‑smooth muscle actin, collagen 1A1 and ROCK1. Collagen 3A1 secretion was also measured by ELISA. Cell proliferation was assessed by the MTT assay under these hypoxic conditions. The results indicated that a specific ROCK inhibitor, Y‑27632, increased HIF1‑α and ROCK1 expression over time in HSC‑T6 cells in response to hypoxia. In addition, knockdown of HIF1‑α inhibited HSC‑T6 proliferation, suppressed collagen 1A1 expression, decreased collagen 3A1 secretion and attenuated ROCK1 expression. Notably, ROCK1 inhibition caused HSC‑T6 quiescence, suppressed collagen secretion and downregulated HIF1‑α expression. Collectively, these findings indicated that the interplay between HIF1‑α and ROCK1 may be a critical factor that regulates cell proliferation and collagen synthesis in rat HSCs under hypoxia.
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Copy and paste a formatted citation
Spandidos Publications style
Hu Y, Hu D, Yu H, Xu W and Fu R: Hypoxia‑inducible factor 1α and ROCK1 regulate proliferation and collagen synthesis in hepatic stellate cells under hypoxia. Mol Med Rep 18: 3997-4003, 2018.
APA
Hu, Y., Hu, D., Yu, H., Xu, W., & Fu, R. (2018). Hypoxia‑inducible factor 1α and ROCK1 regulate proliferation and collagen synthesis in hepatic stellate cells under hypoxia. Molecular Medicine Reports, 18, 3997-4003. https://doi.org/10.3892/mmr.2018.9397
MLA
Hu, Y., Hu, D., Yu, H., Xu, W., Fu, R."Hypoxia‑inducible factor 1α and ROCK1 regulate proliferation and collagen synthesis in hepatic stellate cells under hypoxia". Molecular Medicine Reports 18.4 (2018): 3997-4003.
Chicago
Hu, Y., Hu, D., Yu, H., Xu, W., Fu, R."Hypoxia‑inducible factor 1α and ROCK1 regulate proliferation and collagen synthesis in hepatic stellate cells under hypoxia". Molecular Medicine Reports 18, no. 4 (2018): 3997-4003. https://doi.org/10.3892/mmr.2018.9397
Copy and paste a formatted citation
x
Spandidos Publications style
Hu Y, Hu D, Yu H, Xu W and Fu R: Hypoxia‑inducible factor 1α and ROCK1 regulate proliferation and collagen synthesis in hepatic stellate cells under hypoxia. Mol Med Rep 18: 3997-4003, 2018.
APA
Hu, Y., Hu, D., Yu, H., Xu, W., & Fu, R. (2018). Hypoxia‑inducible factor 1α and ROCK1 regulate proliferation and collagen synthesis in hepatic stellate cells under hypoxia. Molecular Medicine Reports, 18, 3997-4003. https://doi.org/10.3892/mmr.2018.9397
MLA
Hu, Y., Hu, D., Yu, H., Xu, W., Fu, R."Hypoxia‑inducible factor 1α and ROCK1 regulate proliferation and collagen synthesis in hepatic stellate cells under hypoxia". Molecular Medicine Reports 18.4 (2018): 3997-4003.
Chicago
Hu, Y., Hu, D., Yu, H., Xu, W., Fu, R."Hypoxia‑inducible factor 1α and ROCK1 regulate proliferation and collagen synthesis in hepatic stellate cells under hypoxia". Molecular Medicine Reports 18, no. 4 (2018): 3997-4003. https://doi.org/10.3892/mmr.2018.9397
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