MicroRNA-361-5p Aggravates Acute Pancreatitis by Promoting Interleukin-17A Secretion via Impairment of Nuclear Factor IA-Dependent Hes1 Downregulation.

Abstract

This study set out to explore the potential role of microRNA-361-5p (miR-361-5p) in acute pancreatitis through regulation of interleukin-17A (IL-17A). We first identified the expression of miR-361-5p, IL-17A, nuclear factor IA (NFIA), and hes family bHLH transcription factor 1 (Hes1) in serum samples collected from patients with acute pancreatitis, caerulein-induced mice, and a Th17 cell model. The predicted binding of miR-361-5p to NFIA was confirmed in vitro. Gain- and loss-of-function assays of miR-361-5p and NFIA were employed to elucidate their effects on acute pancreatitis. miR-361-5p promoted Th17 cells to secrete IL-17A and then aggravated acute pancreatitis. miR-361-5p directly targeted NFIA by binding to its promoter region, leading to its downregulation. Overexpression of NFIA reduced Hes1 expression and rescued the promoting effect of miR-361-5p on IL-17A secretion. In summary, miR-361-5p enhances IL-17A secretion from Th17 cells and thus aggravates acute pancreatitis by targeting NFIA and upregulating Hes1.