+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

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



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



Journal of Cellular Biochemistry 120(1): 290-304



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.

(PDF emailed within 0-6 h: $19.90)

Accession: 065845160

Download citation: RISBibTeXText

PMID: 30216510

DOI: 10.1002/jcb.27356


Related references

BRL-44408 maleate, the antagonist of α 2A -adrenoceptor, attenuates endogenous lipopolysacchride-induced acute lung injury through inhibiting the mitogen-activated protein kinase kinase/extracellular regulated protein kinases signaling pathway in mice. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 30(2): 101-106, 2018

Mitogen-activated protein kinase kinase kinase 1 protects against nickel-induced acute lung injury. Toxicological Sciences 104(2): 405-411, 2008

Effects of mitogen-activated protein kinase signaling pathway inhibition on the development of cerulein-induced acute pancreatitis in mice. Pancreas 41(4): 560-570, 2012

Tumor necrosis factor signaling to stress-activated protein kinase /Jun NH2-terminal kinase and p38 Germinal center kinase couples TRAF2 to mitogen-activated protein kinase/ERK kinase kinase 1 and SAPK while receptor interacting protein associates with a mitogen-activated protein kinase kinase kinase upstream of MKK6 and p38. Journal of Biological Chemistry 273(35): 22681-22692, Aug 28, 1998

Tumor necrosis factor signaling to stress-activated protein kinase (SAPK)/Jun NH2-terminal kinase (JNK) and p38. Germinal center kinase couples TRAF2 to mitogen-activated protein kinase/ERK kinase kinase 1 and SAPK while receptor interacting protein associates with a mitogen-activated protein kinase kinase kinase upstream of MKK6 and p38. Journal of Biological Chemistry 273(35): 22681-22692, 1998

Up-regulation of Tight-Junction Proteins by p38 Mitogen-Activated Protein Kinase/p53 Inhibition Leads to a Reduction of Injury to the Intestinal Mucosal Barrier in Severe Acute Pancreatitis. Pancreas 45(8): 1136-1144, 2018

Carbon monoxide protects against oxidant-induced lung injury in mice via the p38 mitogen activated protein kinase pathway. Acta Haematologica (Basel) 103(Supplement 1): 83, 2000

DBM1285 suppresses tumor necrosis factor alpha production by blocking p38 mitogen-activated protein kinase/mitogen-activated protein kinase-activated protein kinase 2 signaling pathway. Journal of Pharmacology and Experimental Therapeutics 334(2): 657-664, 2010

Inorganic lead activates the mitogen-activated protein kinase kinase-mitogen-activated protein kinase-p90(RSK) signaling pathway in human astrocytoma cells via a protein kinase C-dependent mechanism. Journal of Pharmacology and Experimental Therapeutics 300(3): 818-823, 2002

Propofol post-conditioning protects against cardiomyocyte apoptosis in hypoxia/reoxygenation injury by suppressing nuclear factor-kappa B translocation via extracellular signal-regulated kinase mitogen-activated protein kinase pathway. European Journal of Anaesthesiology 28(7): 525-534, 2011

AICAR induces cyclooxygenase-2 expression through AMP-activated protein kinase-transforming growth factor-beta-activated kinase 1-p38 mitogen-activated protein kinase signaling pathway. Biochemical Pharmacology 80(8): 1210-1220, 2010

Mitogen-activated protein kinase-activated protein (MAPKAP) kinase 2 deficiency protects brain from ischemic injury in mice. Journal of Biological Chemistry 277(46): 43968-43972, 2002

Protective Effects of Calcitonin Gene-Related Peptide-Mediated p38 Mitogen-Activated Protein Kinase Pathway on Severe Acute Pancreatitis in Rats. Digestive Diseases and Sciences 2018, 2018

Mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling pathway is required for bryostatin 1-induced differentiation of the human Acute Lymphoblastic Leukemia cell line Reh. Proceedings of the American Association for Cancer Research Annual Meeting 42: 335, 2001

Isotetrandrine protects against lipopolysaccharide-induced acute lung injury by suppression of mitogen-activated protein kinase and nuclear factor-kappa B. Journal of Surgical Research 187(2): 596-604, 2014