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.
Mol Med Rep. 2020 Oct;22(4):3191-3200. doi: 10.3892/mmr.2020.11423. Epub 2020 Aug 7.
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.
肝纤维化（HF）是许多慢性肝病的常见并发症，但主要是由持续的肝炎症或损伤引起的。如果不治疗，HF 会进展并发展为肝硬化，甚至肝细胞癌。然而，HF 的潜在分子机制尚不清楚。本研究旨在探讨 11β-羟甾类脱氢酶-1（11β-HSD1）在肝纤维化发展过程中的作用。使用猪血清诱导大鼠肝纤维化实验模型，评估肝纤维化过程中 11β-HSD1 基因表达水平和酶活性。使用小干扰 RNA 对 LX2-人肝星状细胞（HSCs）中的 11β-HSD1 基因进行敲低，并用过表达质粒进行过表达。用转化生长因子-β1（TGF-β1）刺激 HSCs。比较刺激前后 HSCs 的细胞周期分布、增殖、胶原分泌和 11β-HSD1 基因活性。随着肝纤维化的进展，11β-HSD1 基因表达和活性增加，与典型的肝纤维化标志物呈正相关。11β-HSD1 抑制显著降低纤维化程度。与 N 组相比，pSuper 转染组的细胞增殖增加，G0/G1 期细胞数量减少，S 期和 G2/M 期细胞数量增加。此外，11β-HSD1 的过表达增强了 TGF-β1 诱导的 LX2-HSCs 的激活和结缔组织生长因子的酶活性。11β-HSD1 敲低通过阻断细胞周期的 G0/G1 期抑制细胞增殖，这与 HSC 刺激和 11β-HSD1 酶活性抑制有关。综上所述，肝脏中 11β-HSD1 的表达增加可能部分导致肝纤维化，这可能与 HSC 的激活和增殖有关。
