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

SIRT2 alleviates pre-eclampsia via prompting mitochondrial biogenesis and function

  • Life Sci. 2025 Jun 15:371:123566. doi: 10.1016/j.lfs.2025.123566.
Ruirui Hou 1,  Xiaoyan Yang 2,  Qi Xu 3,  Can Shen 2,  Longbiao Zhang 3,  Binbin Huang 4,  Yuanyuan Yang 2,  Zhen Yu 2,  Zongzhi Yin 5,  Yunxia Cao 6,  Xiaoqing Peng 7
Affiliations

Affiliations

  • 1 School of Pharmacy, Anhui Medical University, Hefei, China; Institute of Mental Health, Suzhou Psychiatric Hospital, The Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu, China; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, Hefei, Anhui, China.
  • 2 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China; The Key National Health Commission Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei, China.
  • 3 School of Pharmacy, Anhui Medical University, Hefei, China; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, Hefei, Anhui, China.
  • 4 The Key National Health Commission Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei, China; Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, Hefei, China; MOE Key Laboratory of Population Health Across Life Cycle, Hefei, China.
  • 5 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China; The Key National Health Commission Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei, China. Electronic address: yinzongzhi@ahmu.edu.cn.
  • 6 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China; The Key National Health Commission Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei, China. Electronic address: caoyunxia5972@ahmu.edu.cn.
  • 7 School of Pharmacy, Anhui Medical University, Hefei, China; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, Hefei, Anhui, China; Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China; The Key National Health Commission Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei, China. Electronic address: pengxiaoqing@ahmu.edu.cn.
PMID: 40118268 DOI: 10.1016/j.lfs.2025.123566
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.

Keywords

Mitochondria/pathology; Mitochondrial dynamics; Pre-eclampsia; Sirtuin 2.

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