SIRT2 alleviates pre-eclampsia via prompting mitochondrial biogenesis and function.

Abstract

Aims

Pre-eclampsia (PE) globally impacts 2–8 % of pregnancies and is a leading cause of neonatal and maternal morbidity and mortality. Recent studies found the association between mitochondrial dysfunction and deficient motility of trophoblast cells in PE. Lower expressions of mitochondrial biogenesis related proteins (i.e. PGC1α, NRF1 and TFAM) and SIRT2 have recently been found. However, the regulative role of SIRT2 on the protein expression and acetylation of PGC1α and its influence on trophoblast migration and invasion in PE have never been investigated.

Materials and methods

The alterations in protein expressions of SIRT2 and PGC1α/NRF1/TFAM were examined in the placenta from pregnant women with and without PE. The role of SIRT2 on mitochondrial biogenesis and mitochondrial morphology/function was explored in trophoblast cell, and the findings were confirmed in the LPS-induced PE mice with adeno-associated virus transfection system.

Key findings

We demonstrated the lower protein expressions of SIRT2 and PGC1α/NRF1/TFAM and mitochondrial dysfunction in PE patients and mice compared with counterparts. Moreover, overexpression of SIRT2 enhanced the protein expressions of PGC1α and deacetylated PGC1α, and further facilitating mitochondrial function and motility of trophoblast cells. In vivo, overexpression of SIRT2 attenuated the PE-like symptoms and adverse pregnancy outcomes in LPS-induced PE mice via promoting mitochondrial biogenesis.

Significance

Above findings suggest that SIRT2 might be a potential interventive target against PE via improving deacetylation of PGC1α and mitochondrial biogenesis and function.