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Hepatic stellate cell is activated by microRNA-181b via PTEN/Akt pathway

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Abstract

Activation of hepatic stellate cells (HSCs) is an essential event in the initiation and progression of liver fibrosis. MicroRNAs have been shown to play a pivotal role in regulating HSC functions such as cell proliferation, differentiation, and apoptosis. Recently, miR-181b has been reported to promote HSCs proliferation by targeting p27. But whether alpha-smooth muscle actin (α-SMA) or collagens could be promoted by miR-181b in activated HSCs is still not clear. Therefore, the understanding of the role of miR-181b in liver fibrosis remains limited. Our results showed that miR-181b expression was increased much higher than miR-181a expression in vitro in transforming growth factor-β1-induced HSC activation as well as in vivo in carbon tetrachloride-induced rat liver fibrosis. Of note, overexpression of miR-181b significantly increased the expressions level of α-SMA and type I collagen, and further promoted HSCs proliferation. Furthermore, phosphatase and tensin homologs deleted on chromosome 10 (PTEN), a negative regulator of PI3K/Akt pathway, were confirmed as a direct target of miR-181b. We demonstrated that miR-181b could suppress PTEN expression and increase Akt phosphorylation in HSCs. Interestingly, the effects of miR-181b on the activation of HSCs were blocked down by Akt inhibitor LY294002. Our results revealed a profibrotic role of miR-181b in HSC activation and demonstrated that miR-181b could activate HSCs, at least in part, via PTEN/Akt pathway.

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Abbreviations

PTEN:

Phosphatase and tensin homolog deleted on chromosome 10

HSCs:

Hepatic stellate cells

miRNAs:

MicroRNAs

ECM:

Extracellular matrix

α-SMA:

Alpha-smooth muscle actin

TGF-β1:

Transforming growth factor-β1

3′-UTR:

3′-Untranslated region

CCl4 :

Carbon tetrachloride

Col1A1:

Alpha-1(I) collagen

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Acknowledgments

The Project was supported by National Natural Science Foundation of China (81000176/H0317, 81100292/H0317), Zhejiang Provincial Natural Science Foundation of China (Y2090326, Y2110634), Wang Bao-En Liver Fibrosis Foundation (Nos. 20100002, 20120127), Department of Science and Technology of Zhejiang Province (2013C37006), Department of Education of Zhejiang Province (Y201326684), Wenzhou Municipal Science and Technology Bureau (Y20100188, Y20120127) and the key disciplines in Colleges and Universities of Zhejiang Province.

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Authors and Affiliations

  1. Wenzhou Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, No. 2 Fuxue Lane, Wenzhou, 325000, Zhejiang, People’s Republic of China

    Jianjian Zheng & Bicheng Chen

  2. Institute of Organ Transplantation, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People’s Republic of China

    Cunzao Wu, Ziqiang Xu & Peng Xia

  3. Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, No. 2 Fuxue Lane, Wenzhou, 325000, Zhejiang, People’s Republic of China

    Peihong Dong & Fujun Yu

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  1. Jianjian Zheng
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  2. Cunzao Wu
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  4. Peng Xia
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  5. Peihong Dong
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  6. Bicheng Chen
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  7. Fujun Yu
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Correspondence to Bicheng Chen or Fujun Yu.

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Zheng, J., Wu, C., Xu, Z. et al. Hepatic stellate cell is activated by microRNA-181b via PTEN/Akt pathway. Mol Cell Biochem 398, 1–9 (2015). https://doi.org/10.1007/s11010-014-2199-8

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  • DOI: https://doi.org/10.1007/s11010-014-2199-8

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