ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Translational and Clinical Endocrinology
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1480453
Short Communication SMYD2 inhibitors have no effect to improve non-alcoholic steatohepatitis in mice
Provisionally accepted
- 1University of Chinese Academy of Sciences, Beijing, China
- 2Chinese Academy of Sciences (CAS), Beijing, Beijing, China
- 3ShanghaiTech University, Shanghai, Shanghai Municipality, China
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Nonalcoholic steatohepatitis (NASH), characterized by progressive liver injury, inflammation and fibrosis, is a leading chronic liver disease worldwide. Pharmacotherapy for NASH is thus urgently needed. Through a strategy of in vivo lineage tracing, it was recently discovered that deletion of a protein methyltransferase SMYD2 has a protective role in hepatic steatosis. In this study, we evaluated the potential therapeutic effect of two SMYD2 inhibitors AZ505 and LLY-507 in a mouse NASH model. The mouse NASH model was induced by a choline-deficient, L-amino acid defined, high-fat diet (CDAHFD) for 12 weeks. SMYD2 inhibitors AZ505 and LLY-507 was administered in the last 4 weeks at dose 10 mg/kg by intraperitoneal injection three times per week respectively. The inhibitory effect of AZ505 and LLY-507 on histone methylation was confirmed with liver samples.CDAHFD was able to induce marked liver fibrosis and inflammation in the mice. However, treatment of the mice with AZ505 and LLY-507 failed to show any improvement in NASH scores, liver damage, liver fibrosis, macrophage infiltration, or hepatic inflammation in mice. In conclusions, our findings suggest that SMYD2 inhibition is not an effective strategy to alleviate NASH at least in mice.
Keywords: SMYD2, non-alcoholic steatohepatitis, liver injury, Fibrosis, Inflammation, Hepatic Steatosis
Received: 14 Aug 2024; Accepted: 12 May 2025.
Copyright: © 2025 Chen, Yang, Zhuo, Zhu, Zhang and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yan Chen, University of Chinese Academy of Sciences, Beijing, China
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