1. Academic Validation
  2. MiR-325-3p Alleviates Acute Pancreatitis via Targeting RIPK3

MiR-325-3p Alleviates Acute Pancreatitis via Targeting RIPK3

  • Dig Dis Sci. 2022 Sep;67(9):4471-4483. doi: 10.1007/s10620-021-07322-6.
Ao Jia 1 Zhen-Wei Yang 1 Ji-Yu Shi 1 Jia-Ming Liu 1 Kun Zhang 2 Yun-Feng Cui 3 4
Affiliations

Affiliations

  • 1 Tianjin Medical University, Tianjin, 300070, China.
  • 2 Department of Surgery, Tianjin Nankai Hospital, Nankai Clinical School of Medicine, 122 Sanwei Road, Nankai District, Tianjin, 300110, China.
  • 3 Tianjin Medical University, Tianjin, 300070, China. nkyycyf@tmu.edu.cn.
  • 4 Department of Surgery, Tianjin Nankai Hospital, Nankai Clinical School of Medicine, 122 Sanwei Road, Nankai District, Tianjin, 300110, China. nkyycyf@tmu.edu.cn.
Abstract

Background and aims: Acute pancreatitis (AP) is an acute inflammatory disease that can lead to death. Mir-325-3p is strongly and abnormally expressed in many diseases, necessitating exploration of its function and mechanism in AP.

Methods: Blood samples from AP patients and mice were analyzed. The expression levels of miR-325-3p in AP patients and mouse were detected. Whether miR-325-3p targets RIPK3 gene was predicted by TargetScan online database and dual luciferase reporter assay. In vitro experiments verified the effect of miR-325-3p overexpression on caerulein-induced MPC83 pancreatic acinar Cancer cell line. In vivo experiments verified the effect of overexpression of miR-325-3p on the disease degree of pancreatic tissues in AP mice.

Results: Analysis of blood samples from AP patients and experiments in mice demonstrated that expression of miR-325-3p was significantly reduced during the process of AP in humans and mice. Predicted using the TargetScan online database and through dual luciferase reporter assay detection, miR-325-3p directly targets the RIPK3 gene. In vitro experiments revealed that overexpression of miR-325-3p reversed caerulein-induced Apoptosis and Necroptosis in MPC83 pancreatic acinar Cancer cell line. We used Z-VAD-FMK to assess Necroptosis and demonstrated that miR-325-3p targets Necroptosis to reduce cell damage. In subsequent experiments in mice, we verified that overexpression of miR-325-3p reduces inflammation, edema, hemorrhage, and necrosis in acute pancreatitis. Characteristic western blot, immunohistochemistry, and transmission electron microscopy results revealed that overexpression of miR-325-3p reduces the severity of acute pancreatitis by inhibiting pancreatic Necroptosis in AP mice.

Conclusions: The current research results indicate that miR-325-3p directly targets RIPK3 and exerts a protective role in mouse AP. Necroptosis is still the primary mechanism of RIPK3 regulation. MiR-325-3p inhibits acute pancreatitis by targeting RIPK3-dependent Necroptosis, which may represent a novel treatment method for acute pancreatitis.

Keywords

Acute pancreatitis; Necroptosis; RIPK3; miR-325-3p.

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