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

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MicroRNA-361-5p Aggravates Acute Pancreatitis by Promoting Interleukin-17A Secretion via Impairment of Nuclear Factor IA-Dependent Hes1 Downregulation
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2021-11-05 , DOI: 10.1021/acs.jmedchem.1c01110
Menglong Song _{1,

2} , Yifan Wang _{2,

3} , Ping Zhou _{1,

2} , Jiandong Wang _{2,

3} , Haidong Xu _{2,

3} , Jun Zheng _{2,

3}

Affiliation

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.

中文翻译：

MicroRNA-361-5p 通过损害核因子 IA 依赖性 Hes1 下调促进白细胞介素 17A 分泌加重急性胰腺炎

本研究旨在通过调节白细胞介素 17A (IL-17A) 探索 microRNA-361-5p (miR-361-5p) 在急性胰腺炎中的潜在作用。我们首先鉴定了从急性胰腺炎患者、caerulein 诱导的小鼠和 a Th17 细胞模型。miR-361-5p 与 NFIA 的预测结合在体外得到证实. 使用 miR-361-5p 和 NFIA 的功能获得和损失测定来阐明它们对急性胰腺炎的影响。miR-361-5p促进Th17细胞分泌IL-17A，进而加重急性胰腺炎。miR-361-5p 通过与其启动子区域结合直接靶向 NFIA，导致其下调。NFIA 的过表达降低了 Hes1 的表达，并挽救了 miR-361-5p 对 IL-17A 分泌的促进作用。总之，miR-361-5p 增强 Th17 细胞分泌 IL-17A，从而通过靶向 NFIA 和上调 Hes1 加重急性胰腺炎。

更新日期：2021-11-25

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