Silenced microRNA-222 suppresses inflammatory response in gestational diabetes mellitus mice by promoting CXCR4

Abstract Objective Gestational diabetes mellitus (GDM) is induced by multiple factors, and the microRNAs (miRNAs) are well-known to be implicated in GDM progression. We aimed to explore the functional mechanisms of miR-222 in the inflammatory response in GDM by mediating C-X-C chemokine receptor type 4 (CXCR4) and NLRP3 inflammasomes. Methods GDM models were established by intraperitoneal injection of streptozocin, and the levels of miR-222 and CXCR4 in GDM patients' placenta tissues as well as GDM mice' placenta and pancreatic tissues were determined. The GDM mice were treated with miR-222 Antagomir/Agomir or overexpressed CXCR4 to evaluate the apoptosis and pathological changes in tissues, and the levels of blood glucose, insulin, biochemical indices, inflammatory factors and inflammasome-related proteins. Importantly, the target relation between miR-222 and CXCR4 was verified. Results MiR-222 was increased while CXCR4 was decreased in GDM patients and mice. The down-regulated miR-222 and up-regulated CXCR4 could promote insulin sensitivity and insulin level, while inhibit apoptosis, inflammation and glucagon level in GDM mice. Moreover, CXCR4 was targeted by miR-222. Conclusion We demonstrated that the silenced miR-222 could suppress inflammatory response in GDM mice by promoting CXCR4 and inactivating NLRP3 inflammasomes, which may contribute to GDM treatment.