Reprod Biol. 2024 Mar;24(1):100841.doi: 10.1016/j.repbio.2023.100841. Epub 2023 Dec 19.

Knockdown of TXNIP alleviates gestational diabetes mellitus by activating autophagy to regulate cell proliferation and apoptosis in high glucose-treated trophoblasts

Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, China; Department of Obstetrics and Gynecology, Affiliated Women’s Hospital of Jiangnan University, Wuxi, China.
  • 2 Department of Obstetrics and Gynecology, Affiliated Women’s Hospital of Jiangnan University, Wuxi, China.
  • 3 Department of Obstetrics and Nanjing, Nanjing Medical University, Nanjing, China.
  • 4 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, China. Electronic address: Yang.Xiaojun@hotmail.com.

Abstract

Dysregulated thioredoxin-interacting protein (TXNIP) has been observed in women with gestational diabetes mellitus (GDM), but the specific role of TXNIP in GDM and the underlying mechanism remain unclear. HTR-8/SVneo cells were treated with high glucose to mimic the injured trophoblasts of GDM. In vitro, TXNIP knockdown was performed by siRNA. RTqPCR was performed to determine the expression of the corresponding genes. Cell proliferation and apoptosis were measured using CCK-8, EdU and Annexin V/PI assays. The autophagosome number was assessed using transmission electron microscopy. The expression of the autophagy substrate sequestosome 1 (P62) was evaluated by immunofluorescence. Autophagy-related proteins, including P62, light chain 3 (LC3)-I, and LC3-II, were analysed by Western blotting. HTR-8/Svneo cells treated with high glucose demonstrated reduced proliferation, increased apoptosis, decreased autophagosome formation and overall decreased autophagy. However, knockdown of TXNIP reversed the effects of HG on HTR-8/Svneo cells. However, the effect of TXNIP knockdown on HG-treated HTR-8/Svneo cells was inhibited by 3-methyladenine (3-MA) (widely used as an inhibitor of autophagy). We concluded that knockdown of TXNIP has the potential to enhance the activity of high glucose-treated human trophoblasts through autophagic activation, thereby improving pregnancy outcomes in patients with GDM.

Keywords: Autophagy; GDM; TXNIP; Trophoblast.

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