USP13 ameliorates metabolic dysfunction-associated steatohepatitis through targeting PTEN

Area of Science:

• Hepatology
• Molecular Biology
• Biochemistry

Background:

• Metabolic dysfunction-associated steatohepatitis (MASH) is a growing health concern with unclear molecular mechanisms.
• The specific role of ubiquitin-specific protease 13 (USP13) in MASH pathogenesis has not been fully elucidated.

Purpose of the Study:

• To investigate the role and mechanism of USP13 in the progression of MASH.
• To determine if USP13 can serve as a therapeutic target for MASH.

Main Methods:

• Established in vitro (THLE-2 cells with palmitate acid) and in vivo (HFFC and MCD diet mice) MASH models.
• Utilized Usp13 overexpression and knockout techniques to assess its functional impact.
• Investigated the molecular interaction between USP13 and PTEN.

Main Results:

• USP13 expression was significantly reduced in MASH models.
• Usp13 overexpression ameliorated liver steatosis, inflammation, and fibrosis in MASH.
• USP13 directly deubiquitinated PTEN, increasing its expression and improving the MASH phenotype.
• PTEN overexpression reversed MASH exacerbation in Usp13 knockout mice.

Conclusions:

• USP13 plays a protective role in MASH by deubiquitinating PTEN.
• The USP13-PTEN signaling pathway is a critical regulator of MASH.
• Targeting the USP13-PTEN axis offers a promising therapeutic strategy for MASH treatment.