Filamin A is overexpressed in non-alcoholic steatohepatitis and contributes to the progression of inflammation and fibrosis.

Ying Lu, Mengzhu Wang, Manyu Zhao, Qianru Zhang, Rui Qian, Zan Hu, Qi Ke, Lin Yu, Liqun Wang, Qinhuai Lai, Zhenmi Liu, Xia Jiang, Ben Zhang, Jinliang Yang, Yuqin Yao

Biochemical and biophysical research communications 2023 Apr 23

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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. Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Ying Lu, Mengzhu Wang, Manyu Zhao, Qianru Zhang, Rui Qian, Zan Hu, Qi Ke, Lin Yu, Liqun Wang, Qinhuai Lai, Zhenmi Liu, Xia Jiang, Ben Zhang, Jinliang Yang, Yuqin Yao. Filamin A is overexpressed in non-alcoholic steatohepatitis and contributes to the progression of inflammation and fibrosis. Biochemical and biophysical research communications. 2023 Apr 23;653:93-101