TM4SF5-mediated KEAP1 Regulation in Hepatocytes Irrelevant to NRF2 Expression and Activity Promotes Oxidative Stress and Inflammation to Develop Metabolic Dysfunction-Associated Steatotic Liver Disease

International Journal of Biological Sciences 2026 Open access

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Authors: Eun‐Ae Shin, Haesong Lee, Kyung‐hee Pyo, Wonsik Kim, Soyeon Kim, Jae-Ho Lee, Suwei Jin, Eunmi Kim, Soo-Min Byeon, Dong Joo Kim, Young Jun Cho, Tae Won Kim
+10 more Minjae Ohn, Hyojung Lee, Jeongwon Lee, Jinwook Jeong, Doojin Kim, Jie Zheng, Han Bi Lee, Hwi Young Kim, Young‐Joon Surh, Jung Weon Lee
DOI: 10.7150/ijbs.126251
Cited by: 0

Abstract

displayed TM4SF5-induced MASLD phenotypes characterized by elevated Keap1, regardless of Nrf2 expression or activity. These findings were more obvious than for mice with Nrf2 mutation alone. Notably, suppression of Keap1 alone nullified the MASLD-promoting effects of TM4SF5. Taken together, these data demonstrate that TM4SF5 can modulate KEAP1 independently of NRF2, identifying TM4SF5-mediated KEAP1 stabilization as a potential therapeutic target for MASLD.

Fields of Study & Subjects

Genomics phytochemicals and oxidative stress Liver Disease Diagnosis and Treatment Liver physiology and pathology

Publication details

Journal / source
International Journal of Biological Sciences
Volume
22
Issue
3
Pages
1103–1125
Publication date
1 January 2026
Language
EN