SKIL/SnoN attenuates TGF-β1/SMAD signaling-dependent collagen synthesis in hepatic fibrosis

被引:4
|
作者
Chi, Cheng [1 ,2 ]
Liang, Xifeng [2 ,3 ]
Cui, Tianyu [1 ]
Gao, Xiao [1 ]
Liu, Ruixia [1 ]
Yin, Chenghong [1 ]
机构
[1] Capital Med Univ, Beijing Obstet & Gynecol Hosp, Beijing Maternal & Child Hlth Care Hosp, Cent Lab, Beijing, Peoples R China
[2] Jining Med Univ, Sch Nursing, Jining, Shandong, Peoples R China
[3] Weifang Med Univ, Sch Nursing, Weifang, Shandong, Peoples R China
来源
BIOMOLECULES AND BIOMEDICINE | 2023年 / 23卷 / 06期
关键词
Ski-related novel protein N (SnoN); SKIL; transforming growth factor-beta 1 (TGF-beta 1); hepatic fibrosis (HF); bioinformatics; STELLATE CELLS; PROMOTES; CANCER; LIVER; SNON; PROGRESSION; EXPRESSION; INHIBITOR;
D O I
10.17305/bb.2023.9000
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The ski-related novel protein N (SnoN), encoded by the SKIL gene, has been shown to negatively regulate transforming growth factor-beta 1 (TGF-beta 1) signaling pathway. However, the roles of SnoN in hepatic stellate cell (HSC) activation and hepatic fibrosis (HF) are still unclear. To evaluate the role of SnoN in HF, we combined bulk RNA sequencing analysis and single-cell RNA sequencing analysis to analyze patients with HF. The role of SKIL/SnoN was verified using liver samples from rat model transfected HSC-T6 and LX-2 cell lines. Immunohistochemistry, immunofluorescence, PCR, and western blotting techniques were used to demonstrate the expression of SnoN and its regulatory effects on TGF-beta 1 signaling in fibrotic liver tissues and cells. Furthermore, we constructed a competitive endogenous RNA regulatory network and potential drug network associated with the SKIL gene. We identified the SKIL gene as a differentially expressed gene in HF. SnoN protein was found to be widely expressed in the cytoplasm of normal hepatic tissues, whereas it was almost absent in HF tissues. In the rat group subjected to bile duct ligation (BDL), SnoN protein expression decreased, while TGF-beta 1, collagen III, tissue inhibitor of metalloproteinase 1 (TIMP-1), and fibronectin levels increased. We observed the interaction of SnoN with p-SMAD2 and p-SMAD3 in the cytoplasm. Following SnoN overexpression, apoptosis of HSCs was promoted, and the expression of HF-associated proteins, including collagen I, collagen III, and TIMP-1, was reduced. Conversely, downregulation of SnoN inhibited HSC apoptosis, increased collagen III and TIMP-1 levels, and decreased matrix metalloproteinase 13 (MMP-13) expression. In conclusion, SnoN expression is downregulated in fibrotic livers and could attenuate TGF-beta 1/SMADs signaling-dependent de-repression of collagen synthesis.
引用
收藏
页码:1014 / 1025
页数:12
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