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Ubiquitin-specific protease 14 regulates cardiac hypertrophy progression by increasing GSK-3β phosphorylation

Ningning Liu1, Renjie Chai1, Bin Liu1

  • 1Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510260, China.

Biochemical and Biophysical Research Communications
|August 23, 2016
PubMed

Insights

Ubiquitin-specific protease 14 (USP14) drives cardiac hypertrophy by increasing GSK-3β phosphorylation. Inhibiting USP14 may offer a new therapeutic strategy for treating this heart condition.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Biochemistry

Background:

  • Cardiac hypertrophy is a significant risk factor for cardiovascular diseases and mortality.
  • Ubiquitin-proteasome system signaling pathways are increasingly recognized for their role in regulating cardiac hypertrophy.
  • Identifying novel therapeutic targets is crucial for managing cardiac hypertrophy.

Purpose of the Study:

  • To investigate the role of ubiquitin-specific protease 14 (USP14) in cardiac hypertrophy.
  • To determine if USP14 could serve as a therapeutic target for cardiac hypertrophy.
  • To elucidate the signaling pathway through which USP14 influences cardiac hypertrophy.

Main Methods:

  • Utilized an animal model of abdominal aorta constriction to assess USP14 expression.
  • Employed an angiotensin II (AngII)-induced primary neonatal rat cardiomyocyte hypertrophy model.
  • Investigated the effects of reduced USP14 deubiquitinase activity and USP14 knockdown on cardiac hypertrophy markers and GSK-3β phosphorylation.

Main Results:

  • USP14 expression was elevated in both animal and cellular models of cardiac hypertrophy.
  • Reduced USP14 activity or expression led to decreased levels of the myocardial hypertrophy marker β-MHC.
  • USP14 inhibition resulted in decreased phosphorylation of GSK-3β, a key signaling molecule.

Conclusions:

  • USP14 plays a critical role in mediating the development of cardiac hypertrophy.
  • USP14 promotes cardiac hypertrophy by enhancing GSK-3β phosphorylation.
  • USP14 inhibition presents a potential novel therapeutic strategy for cardiac hypertrophy treatment.

Keywords:
Cardiac hypertrophyDeubiquitinaseGSK-3βUSP14

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