LOXL2 in non‐alcoholic Steatohepatitis (NASH): Insights into fibrosis pathogenesis and therapeutic potential

Author:

Immanuel Joys Rachel1,Kumar Rajnish2,Agrahari Ashish Kumar13ORCID,Asthana Shailendra1

Affiliation:

1. Computational Biophysics and CADD group, Computational and Mathematical Biology Center (CMBC) Translational Health Science and Technology Institute (THSTI) Faridabad India

2. Indian Institute of Technology (BHU) Varanasi Varanasi India

3. Department of Physics and Astronomy Clemson University Clemson South Carolina USA

Abstract

AbstractLiver fibrosis involves increased extracellular matrix (ECM) deposition, with lysyl oxidase‐like 2 (LOXL2) emerging as a key player due to its upregulation in fibrotic tissue. As a member of the lysyl oxidase protein family, LOXL2 contributes to ECM accumulation and remodelling through fibre cross‐linking. Its aberrant expression in non‐alcoholic steatohepatitis (NASH) implicates it in liver fibrosis. LOXL2 promotes fibrosis by activating hepatic stellate cells, cross‐linking ECM proteins, and influencing oxidative stress, inflammation and lipid metabolism. Preclinical studies on LOXL2 inhibitors show promise in reducing fibrosis and improving liver function. Ongoing clinical trials further highlight LOXL2 as a potential anti‐fibrotic target. However, challenges such as species differences, tissue‐specific effects and the complexity of NASH pathogenesis require additional research. Understanding LOXL2's role in NASH will aid in developing effective treatments for NASH‐related fibrosis and liver damage.

Publisher

Wiley

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