microRNA-542-5p protects against acute lung injury in mice with severe acute pancreatitis by suppressing the mitogen-activated protein kinase signaling pathway through the negative regulation of P21-activated kinase 1.

Abstract

Severe acute pancreatitis (SAP) is a condition associated with high rates of mortality and lengthy hospital stays. In the current study, SAP mouse models were established in BALB/c wild-type and P21-activated kinase 1 (PAK1) knockdown mice with the objective of determining the expression of microRNA-542-5p (miR-542-5p) and the subsequent elucidation of the mechanism by which it influences acute lung injury (ALI) by mediating mitogen-activated protein kinase (MAPK) signaling and binding to PAK1. The targeting relationship between miR-542-5p and PAK1 was verified using the bioinformatics prediction website and by the means of a dual-luciferase reporter assay. Following the SAP model establishment, the mice were assigned into various groups with the introduction of different mimic and inhibitors in an attempt to investigate the effects involved with miR-542-5p on inflammatory reactions among mice with SAP-associated ALI. Our results indicated that PAK1 was targeted and negatively mediated by miR-542-5p. Mice with SAP-associated ALI exhibited an increased wet-to-dry weight ratio, myeloperoxidase activity, serum amylase activity, TNF-α, interleukin-1 beta (IL-1β), and intercellular adhesion molecule-1 (ICAM-1) contents, p-p38MAPK, p-ERK1/2, and p-JNK protein levels as well as PAK1 positive expression, while decreased miR-542-5p levels were observed. Functionally, overexpression of miR-542-5p improves ALI in mice with SAP via inhibition of the MAPK signaling pathway by binding to PAK1.Based on the evidence from experimental models, miR-542-5p was shown to improve ALI among mice with SAP, while suggesting that the effect may be related to the inactivation of the MAPK signaling pathway and downregulation of PAK1 gene. Thus, miR-542-5p could serve as a promising target for ALI treatment.

• Authors: Xing-Mao Wu, Kai-Qiang Ji, Hai-Yuan Wang, Yang Zhao, Jia Jia, Xiao-Peng Gao, Bin Zang
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 120 Issue 1 Pg. 290-304 (01 2019) ISSN: 1097-4644 [Electronic] United States
• PMID: 30216510 (Publication Type: Journal Article, Retracted Publication)
• Copyright: © 2018 Wiley Periodicals, Inc.

Chemical References

• IL1B protein, mouse
• Icam1 protein, mouse
• Interleukin-1beta
• MIRN542 microRNA, mouse
• MicroRNAs
• Tumor Necrosis Factor-alpha
• Intercellular Adhesion Molecule-1
• Peroxidase
• Pak1 protein, mouse
• p21-Activated Kinases
• Mitogen-Activated Protein Kinases
• p38 Mitogen-Activated Protein Kinases
• Amylases

Topics

• Acute Lung Injury (complications, metabolism)
• Amylases (blood)
• Animals
• Disease Models, Animal
• Edema (metabolism)
• Gene Knockdown Techniques
• Intercellular Adhesion Molecule-1 (metabolism)
• Interleukin-1beta (metabolism)
• MAP Kinase Signaling System
• Male
• Mice
• Mice, Inbred BALB C
• MicroRNAs (metabolism)
• Mitogen-Activated Protein Kinases (metabolism)
• NIH 3T3 Cells
• Pancreatitis (complications, metabolism)
• Peroxidase (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)
• p21-Activated Kinases (genetics, metabolism)
• p38 Mitogen-Activated Protein Kinases (metabolism)