Year: 2025
Type: article
Abstract: Fibroblast growth factor 9 (FGF9) plays a key role in development and cardioprotection, yet its function in diabetic cardiomyopathy (DCM) remains unclear. In a high-fat diet/streptozotocin (HFD/STZ)-induced DCM model, FGF9 attenuated cardiac hypertrophy, fibrosis, and systolic dysfunction, effects abolished in cardiomyocyte-specific Nrf2 knockout mice. Mechanistically, FGF9 restored AMPK activity and promoted autophagy, enhancing p62-mediated degradation of Keap1 and nuclear translocation of Nrf2. In neonatal rat cardiomyocytes (NRCMs), FGF9 reversed high glucose and palmitate (HG + PA)-induced suppression of AMPK phosphorylation, autophagic flux, and Nrf2 signaling. AAV9-mediated expression of wild-type AMPK (AMPKWT) or a dominant-negative AMPK mutant (AMPKT172A) confirmed that AMPK activation was essential for FGF9-induced Nrf2 activation. Functionally, FGF9 reduced lipid accumulation, preserved mitochondrial integrity, and alleviated oxidative stress. FGF9 ameliorates DCM via non-canonical autophagy-dependent activation of Nrf2, mediated by AMPK. These findings position FGF9 as a potential therapeutic target for diabetic myocardial injury. FGF9 alleviates cardiac hypertrophy, fibrosis, and dysfunction in diabetic models by activating Nrf2 through AMPK-dependent, autophagy-mediated degradation of Keap1
Source: Communications Biology
Institution: Ningbo University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,190
Funders: National Natural Science Foundation of China, Higher Education Discipline Innovation Project, Natural Science Foundation of Ningbo, Medical Science and Technology Project of Zhejiang Province, Natural Science Foundation of Zhejiang Province, Science and Technology Program of Zhejiang Province
OpenAlex ID: W4416668517