Uhrf1 regulates H3K9me2 modification of mTOR to inhibit the effect of autophagy in myocardial ischemia-reperfusion injury

The regulation of mTOR and the dimethylation of histone H3 on lysine 9 (H3K9me2) H3K9me2 by Uhrf1 and the mechanism of autophagy regulation in myocardial ischemia-reperfusion injury (MIRI) were studied in vivo and in vitro. An in vitro I/R injury model was established using the primary mouse cardiomyocytes treated with H2O2. Subsequent analysis by qRT-PCR, western blot, and immunofluorescence indicated that overexpression of Uhrf1 significantly inhibited apoptosis of the H2O2-treated cardiomyocytes, reduced expression of apoptosis factors caspase-3 and Bax, and increased expression of apoptosis inhibitory factor Bcl-2. Furthermore, Uhrf1 was found to increase cardiomyocyte proliferation and promote the expression of mTOR, while the four expression peaks of H3K9me2 on the mTOR gene were inhibited by overexpression of Uhrf1. The expression of autophagy factors LC3, Beclin-1, and p-mTOR in Uhrf1-overexpressed cardiomyocytes was dramatically increased, and P62 expression was dramatically decreased. When an H3K9me2 inhibitor was added to the Uhrf1-knockdown cardiomyocytes, the expression of mTOR was increased, the expression of LC3, Beclin-1, and p-mTOR was decreased, and P62 expression was significantly increased. In the present study, Uhrf1 exhibits a protective function in MIRI, reducing the apoptosis of cardiomyocytes while increasing their proliferation and viability

Automated summary

The study revealed that Uhrf1 plays a protective role in myocardial ischemia-reperfusion injury (MIRI) by regulating mTOR and H3K9me2, promoting cardiomyocyte proliferation and reducing apoptosis.