Department of Infectious Disease, Zhejiang Provincial People's Hospital and People's Hospital Affiliated of Hangzhou Medical College, No. 158 Shangtang Road, Hangzhou, 310014, Zhejiang, China.
Graduate School of Clinical Medicine, Bengbu Medical College, Bengbu, 233000, Anhui, China.
Hum Cell. 2021 May;34(3):759-770. doi: 10.1007/s13577-021-00498-z. Epub 2021 Feb 11.
Liver fibrosis is a chronic liver injury that leads to liver cirrhosis and liver cancer. Ring finger protein 20 (RNF20), also named as E3 ubiquitin-protein ligase BRE1A, has been reported to be involved in chronic liver diseases. However, the role of RNF20 in liver fibrosis remains unclear. To mimic liver fibrosis in vitro, LX-2 cells were treated with TGF-β. Gene and protein expressions were detected by RT-qPCR and western blot, respectively. The mechanism by which RNF20 mediated the progression of liver fibrosis was explored by bioinformatics analysis. Finally, in vivo mouse model of liver fibrosis was established to detect the function of RNF20. The results indicated that TGF-β-induced increase of cell viability and migration was significantly reversed by RNF20 overexpression. Consistently, overexpression of RNF20 significantly reversed TGF-β-induced activation of fibrotic proteins in LX-2 cells. Meanwhile, VEGFA, TNF-α and IL-6 were found to be the downstream targets of RNF20 in LX-2 cells. Moreover, RNF20 overexpression notably inhibited the progression of liver fibrosis via ubiquitination of H2B. Finally, RNF20 upregulation significantly attenuated the symptom of liver fibrosis in vivo. In summary, overexpression of RNF20 significantly inhibited the progression of liver fibrosis in vitro and in vivo. Therefore, RNF20 might serve as a new target for the treatment of liver fibrosis.
肝纤维化是一种慢性肝损伤，可导致肝硬化和肝癌。指环蛋白 20（RNF20），也称为 E3 泛素蛋白连接酶 BRE1A，据报道与慢性肝病有关。然而，RNF20 在肝纤维化中的作用尚不清楚。为了在体外模拟肝纤维化，用 TGF-β处理 LX-2 细胞。分别通过 RT-qPCR 和 Western blot 检测基因和蛋白表达。通过生物信息学分析探讨了 RNF20 介导肝纤维化进展的机制。最后，建立了体内肝纤维化小鼠模型来检测 RNF20 的功能。结果表明，RNF20 的过表达显著逆转了 TGF-β诱导的细胞活力和迁移增加。一致地，RNF20 的过表达显著逆转了 TGF-β诱导的 LX-2 细胞中纤维化蛋白的激活。同时，在 LX-2 细胞中发现 VEGFA、TNF-α 和 IL-6 是 RNF20 的下游靶标。此外，RNF20 的过表达通过 H2B 的泛素化显著抑制肝纤维化的进展。最后，RNF20 的上调显著减轻了体内肝纤维化的症状。总之，RNF20 的过表达显著抑制了体外和体内肝纤维化的进展。因此，RNF20 可能成为治疗肝纤维化的新靶点。
