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RNA-binding protein ZMAT3 protects against MASLD by regulating SEPT11 mRNA stability

Lei Sun1, Zhiwei Huang1, Ankang Wang2

  • 1Department of General Surgery (Hepatobiliary Surgery), Department of Biliary-Pancreatic Center, The Affiliated Hospital, Southwest Medical University, Luzhou 646000, China.

Cellular Signalling
|June 17, 2026
PubMed
Abstract

Insights

Zinc finger matrin-type protein 3 (ZMAT3) protects against metabolic dysfunction-associated steatotic liver disease (MASLD). ZMAT3 downregulation worsens MASLD, while its overexpression offers therapeutic potential by regulating lipid metabolism and inflammation.

Area of Science:

  • Hepatology
  • Molecular Biology
  • Metabolic Disorders

Background:

  • Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing hepatic disorder linked to metabolic syndrome.
  • The role of Zinc finger matrin-type protein 3 (ZMAT3), an RNA-binding protein, in MASLD pathogenesis remains unclear.

Purpose of the Study:

  • To investigate the function of ZMAT3 in MASLD.
  • To explore ZMAT3's impact on lipid metabolism and related signaling pathways in MASLD.

Main Methods:

  • Established a murine MASLD model with hepatocyte-specific ZMAT3 overexpression using a choline-deficient amino acid (CDAA) diet.
  • Utilized in vitro models with AML12 hepatocytes treated with free fatty acids to assess ZMAT3 effects.
  • Identified SEPT11 as a ZMAT3 interacting partner and employed molecular biology assays.

Main Results:

  • ZMAT3 expression was decreased in early-stage MASLD liver tissues and disease models.
  • ZMAT3 overexpression in AML12 cells reduced lipid accumulation and metabolic disturbances.
  • Hepatic ZMAT3 overexpression in MASLD mice attenuated liver injury, inflammation, and lipid accumulation.
  • ZMAT3 regulates SEPT11 mRNA stability, impacting the RhoA/ROCK1/AMPK/SREBP-1c pathway involved in MASLD.

Conclusions:

  • ZMAT3 functions as a protective factor in MASLD.
  • ZMAT3 influences lipid metabolism and the SEPT11/RhoA/ROCK1/AMPK/SREBP-1c pathway.
  • ZMAT3 presents a potential therapeutic target for MASLD.
Keywords:
Fat acid metabolismMASLDTherapeutic targetZMAT3mRNA stability

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