Inhibition of ATP1V6G3 prompts hepatic stellate cell senescence with reducing ECM by activating Notch1 pathway to alleviate hepatic fibrosis.

Xiao-Pei Xue, Yu Sheng, Qi-Qi Ren, Shi-Meng Xu, Min Li, Zhao-Xiu Liu, Cui-Hua Lu

Department Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China; Department Gastroenterology, Rugao Hospital of traditional Chinese Medicine, Nantong 226500, China.Department Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China; Department Gastroenterology, Rugao Hospital of traditional Chinese Medicine, Nantong 226500, China. · pubmed

Paper

Abstract

Liver fibrosis is characterized by an excessive reparative response to various etiological factors, with the activated hepatic stellate cells (aHSCs) leading to extracellular matrix (ECM) accumulation. Senescence is a stable growth arrest, and the senescence of aHSCs is associated with the degradation of ECM and the regression of hepatic fibrosis, making it a promising approach for managing hepatic fibrosis. The role and specific mechanisms by which V-Type Proton ATPase Subunit G 3 (ATP6V1G3) influences senescence in activated HSCs during liver fibrosis remain unclear. Our preliminary results reveal upregulation of ATP6V1G3 in both human fibrotic livers and murine liver fibrosis models. Additionally, ATP6V1G3 inhibition induced senescence in aHSCs in vitro. Moreover, suppressing Notch1 reversed the senescence caused by ATP6V1G3 inhibition in HSCs. Thus, targeting ATP6V1G3, which appears to drive HSCs senescence through the Notch1 pathway, emerges as a potential therapeutic strategy for hepatic fibrosis.

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

The paper addresses the senescence of hepatic stellate cells (HSCs) and its role in liver fibrosis, which is a condition associated with aging. By exploring the mechanisms of ATP6V1G3 inhibition and its effects on HSC senescence through the Notch1 pathway, the research contributes to understanding potential therapeutic strategies that could mitigate age-related liver fibrosis. However, while it presents solid findings, the impact is limited as it primarily focuses on a specific disease mechanism rather than broader implications for longevity or aging as a whole.

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