The role of chemerin in the regulation of cGAS‐STING pathway in gestational diabetes mellitus placenta. Issue 3 (14th February 2023) - Zhou, Xuan
Abstract: Recent studies already confirmed that placenta mitochondrial dysfunction is associated with the progression of gestational diabetes mellitus (GDM). Besides, a possible relationship between adipokine chemerin and disulfide‐bond A oxidoreductase‐like protein (DsbA‐L) had been revealed, whereas the potential interaction remains unclear. In addition, very little is still known about the cyclic GMP‐AMP synthase (cGAS)‐stimulator of interferon genes (STING) signaling pathway and its mechanisms of action in the context of GDM. The present study aims to investigate the underlying mechanism of cGAS‐STING pathway and its regulatory relationship with chemerin in GDM. A total of 50 participants, including 25 cases of GDM patients and 25 pregnant women with normal glucose tolerance, were enrolled, and their placenta tissues at term labor were collected. Besides, an insulin resistance cell model was established on the human trophoblastic cell line to explore the molecular mechanism of chemerin on cGAS‐STING pathway. Results showed that there were mitochondrial pathological changes in GDM placenta, accompanied by the decreased expression of DsbA‐L, increased level of chemerin, and the activation of cGAS‐STING pathway. In the insulin resistant cell model, overexpression of chemerin upregulated protein expression of DsbA‐L, and recombinant chemerin presented time‐dependent inhibition on the cGAS‐STING pathway, but this effect was not dependent on DsbA‐L. In conclusion, elevated chemerin is probably a protective mechanism, which may be a potential therapeutic strategy for GDM. Abstract : Schematic diagram of the role of chemerin in regulating the cGAS‐STING signaling pathway activated in GDM. Placental mitochondria are found swollen in GDM, accompanied by the decreased expressions of DsbA‐L and PGC‐1α, and the activation of cGAS‐STING pathway. Additionally, elevated chemerin has a positive effect on the expression of DsbA‐L and can regulate the cGAS‐STING pathway in the HTR‐8/SVneo cell model.