Open AccessPKM2 promotes angiotensin‐II‐induced cardiac remodelling by activating TGF‐β/Smad2/3 and Jak2/Stat3 pathways through oxidative stress
Author(s) -
Zhang Xiyu,
Zheng Cuiting,
Gao Zhenqiang,
Wang Lingling,
Chen Chen,
Zheng Yuanyuan,
Meng Yan
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.17007
Subject(s) - pkm2 , angiotensin ii , oxidative stress , cardiac fibrosis , cardiac function curve , microbiology and biotechnology , fibrosis , transforming growth factor , ventricular remodeling , glycolysis , regulator , signal transduction , chemistry , heart failure , medicine , biology , pyruvate kinase , biochemistry , metabolism , receptor , gene
Hypertensive cardiac remodelling is a common cause of heart failure. However, the molecular mechanisms regulating cardiac remodelling remain unclear. Pyruvate kinase isozyme type M2 (PKM2) is a key regulator of the processes of glycolysis and oxidative phosphorylation, but the roles in cardiac remodelling remain unknown. In the present study, we found that PKM2 was enhanced in angiotensin II (Ang II)‐treated cardiac fibroblasts and hypertensive mouse hearts. Suppression of PKM2 by shikonin alleviated cardiomyocyte hypertrophy and fibrosis in Ang‐II‐induced cardiac remodelling in vivo. Furthermore, inhibition of PKM2 markedly attenuated the function of cardiac fibroblasts including proliferation, migration and collagen synthesis in vitro. Mechanistically, suppression of PKM2 inhibited cardiac remodelling by suppressing TGF‐β/Smad2/3, Jak2/Stat3 signalling pathways and oxidative stress. Together, this study suggests that PKM2 is an aggravator in Ang‐II‐mediated cardiac remodelling. The negative modulation of PKM2 may provide a promising therapeutic approach for hypertensive cardiac remodelling.