11β‑hydroxysteroid dehydrogenase‑1 is associated with the activation of hepatic stellate cells in the development of hepatic fibrosis

Xiao,Wei; Lu,Meng‑Hou; Rong,Peng‑Fei; Zhang,Hao‑Ye; Gong,Jian; Peng,Ying‑Qiong; Gong,Huan‑Yu; Liu,Zhen‑Guo

doi:10.3892/mmr.2020.11423

11β‑hydroxysteroid dehydrogenase‑1 is associated with the activation of hepatic stellate cells in the development of hepatic fibrosis

Authors:
- Wei Xiao
- Meng‑Hou Lu
- Peng‑Fei Rong
- Hao‑Ye Zhang
- Jian Gong
- Ying‑Qiong Peng
- Huan‑Yu Gong
- Zhen‑Guo Liu
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Affiliations: Department of Infectious Disease, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China, Department of Infectious Disease, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China
Published online on: August 7, 2020 https://doi.org/10.3892/mmr.2020.11423
Pages: 3191-3200
Copyright: © Xiao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hepatic fibrosis (HF) is a common complication of numerous chronic liver diseases, but predominantly results from persistent liver inflammation or injury. If left untreated, HF can progress and develop into liver cirrhosis and even hepatocellular carcinoma. However, the underlying molecular mechanisms of HF remain unknown. The present study aimed to investigate the role of 11β‑hydroxysteroid dehydrogenase‑1 (11β‑HSD1) during the development of hepatic fibrosis. An experimental rat model of liver fibrosis was induced using porcine serum. 11β‑HSD1 gene expression levels and enzyme activity during hepatic fibrogenesis were assessed. 11β‑HSD1 gene knockdown using small interfering RNA and overexpression were performed in LX2‑human hepatic stellate cells (HSCs). HSCs were stimulated with transforming growth factor‑β1 (TGF‑β1). Cell cycle distribution, proliferation, collagen secretion and 11β‑HSD1 gene activity in HSCs were compared before and after stimulation. As hepatic fibrosis progressed, 11β‑HSD1 gene expression and activity increased, indicating a positive correlation with typical markers of liver fibrosis. 11β‑HSD1 inhibition markedly reduced the degree of fibrosis. The cell proliferation was increased, the number of cells in the G0/G1 phase decreased and the number of cells in the S and G2/M phases increased in the pSuper transfected group compared with the N group. In addition, the overexpression of 11β‑HSD1 enhanced the TGF‑β1‑induced activation of LX2‑HSCs and enzyme activity of connective tissue growth factor. 11β‑HSD1 knockdown suppressed cell proliferation by blocking the G0/G1 phase of the cell cycle, which was associated with HSC stimulation and inhibition of 11β‑HSD1 enzyme activity. In conclusion, increased 11β‑HSD1 expression in the liver may be partially responsible for hepatic fibrogenesis, which is potentially associated with HSC activation and proliferation.

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