Up-Regulation of microRNA-185-5p Alleviates Placental Inflammatory Response in Gestational Diabetes Mellitus by Regulating CDC42

Gestational diabetes mellitus (GDM) is a common pregnancy-related disorder characterized by Insulin resistance, chronic inflammation, and placental dysfunction. MicroRNAs (miRNAs) are important regulators of placental development and immune homeostasis. This study investigates the role of miR-185-5p in GDM-associated placental inflammation via the CDC42-JNK/P38 MAPK-ATF2 pathway. CDC42 was identified as a predicted miR-185-5p target using public databases. Placental tissues from GDM patients and controls were analyzed for miR-185-5p and CDC42 expression by RT-qPCR, and direct binding was verified by dual-luciferase assay. A high-glucose-induced HTR8/SVneo trophoblast model was used to test the effects of miR-185-5p and CDC42 modulation on proliferation, Apoptosis, and cytokine release. In vivo, a GDM mouse model was used to evaluate placental inflammation, structure, and signaling changes after intervention. miR-185-5p was downregulated and CDC42 upregulated in GDM placentas, with a significant inverse correlation. miR-185-5p directly bound to the 3'-UTR of CDC42. In high-glucose-treated HTR8/SVneo cells, upregulation of miR-185-5p or silencing of CDC42 reversed glucose-induced proliferation inhibition, reduced Apoptosis, and suppressed TNF-α, IL-6, and IL-1β levels. In GDM mice, miR-185-5p overexpression or CDC42 knockdown significantly reduced placental and serum pro-inflammatory cytokine expression, suppressed phosphorylation of JNK and p38 MAPK, and downregulated downstream ATF2. miR-185-5p targets CDC42 to regulate the JNK/P38 MAPK-ATF2 pathway, thereby attenuating placental inflammation in GDM. This axis may contribute to the chronic inflammatory mechanisms underlying GDM-related placental dysfunction.

CDC42; MAPK signaling pathway; gestational diabetes mellitus (GDM); miR‐185‐5p; placental inflammation.