FLNA公司
菲拉明
炎症
肝星状细胞
纤维化
脂肪性肝炎
癌症研究
生物
基因敲除
脂肪肝
细胞生物学
免疫学
内分泌学
内科学
医学
细胞
细胞培养
疾病
遗传学
细胞骨架
作者
Ying Lü,Mengzhu Wang,Mengyuan Zhao,Qianru Zhang,Rui Qu,Zan Hu,Ke Qin,Lin Yu,Liqun Wang,Qinhuai Lai,Zhenmi Liu,Zhenzhou Lü,Ben Zhang,Jinliang Yang,Yuqin Yao
标识
DOI:10.1016/j.bbrc.2023.02.048
摘要
Non-alcoholic steatohepatitis (NASH) is a chronic and progressive liver disease characterized by steatosis, inflammation, and fibrosis. Filamin A (FLNA), an actin-binding protein, is involved in various cell functions, including the regulation of immune cells and fibroblasts. However, its role in the development of NASH through inflammation and fibrogenesis is not fully understood. In this study, we found that FLNA expression was increased in liver tissues of patients with cirrhosis and mice with non-alcoholic fatty liver disease (NAFLD)/NASH and fibrosis. Immunofluorescence analysis showed that FLNA was primarily expressed in macrophages and hepatic stellate cells (HSCs). Knocking down of FLNA by specific shRNA in phorbol-12-myristate-13-acetate (PMA)-derived THP-1 macrophages reduced lipopolysaccharide (LPS)-stimulated inflammatory response. The decreased mRNA levels of inflammatory cytokines and chemokines and suppression of the STAT3 signaling were observed in FLNA-downregulated macrophages. In addition, knockdown of FLNA in immortalized human hepatic stellate cells (LX-2 cells) resulted in decreased mRNA levels of fibrotic cytokines and enzymes involved in collagen synthesis, as well as increased levels of metalloproteinases and pro-apoptotic proteins. Overall, these results suggest that FLNA may contribute to the pathogenesis of NASH through its role in the regulation of inflammatory and fibrotic mediators.
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