MiR-214-3p targets RIPK1 to regulate pyroptosis and vascular endothelial function in diabetic ketoacidosis: mechanistic insights

Backgrounds: MicroRNAs (miRNAs) exhibit essential effects on the occurrence and progress of diabetes mellitus (DM) and DM complications. However, the detailed role of miRNAs in diabetic ketoacidosis (DKA) is rarely reported.

Objective: The present work focused on the role of miR-214-3p on DKA and the detailed mechanisms.

Methods: First, macrophages were isolated from the venous blood of DKA patients, and ELISA was employed to determine the serum levels of inflammatory factors, serum macrophage numbers by flow cytometry, and macrophage miR-214-3p expression levels determined through PCR.. Subsequently, miR-214-3p was overexpressed in macrophages to detect macrophage proliferation, Apoptosis, Pyroptosis and inflammatory factor secretion. A dual luciferase reporter was used to analyze the downstream targets of miR-214-3p. Finally, macrophages overexpressing miR-214-3p were co-cultured with Human Umbilical Vein Endothelial Cells (HUVECs) to detect the effects of HUVECs proliferation, Apoptosis, and angiogenesis and barrier function.

Results: First, there is an elevation in serum inflammatory factors and a reduction in miR-214-3p levels in serum macrophages among DKA patients, and overexpression of miR-214-3p by macrophages promotes their proliferation, inhibits their Pyroptosis, and reduces the secretion of inflammatory factors. In addition, Receptor-interacting protein kinase 1 (RIPK1) was predicted to be a target of miR-214-3p. Finally, co-culture of macrophages overexpressing miR-214-3p with HUVECs promoted HUVECs proliferation, inhibited Apoptosis, and facilitated the tube-forming ability and repaired the barrier function of HUVECs.

Conclusion: MiR-214-3p targets RIPK1 and regulates vascular endothelial function in diabetic ketoacidosis, suggesting that miR-214-3p has the potential to be a novel marker for the treatment of DKA.

Diabetic ketoacidosis; HUVECs Function; Macrophage; MiR-214-3p; Pyroptosis; RIPK1.