Retracted: 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.

Identification and Validation of Hub Genes in Acute Pancreatitis and Hypertriglyceridemia

“… 31 The inhibition of the MAPK signaling pathway can alleviate lung injury caused by severe pancreatitis. 32 However, whether the inhibition of MAPK signaling alleviates AP is unknown and needs further investigation.…”

New challenges for microRNAs in acute pancreatitis: progress and treatment

“…The results of dual-luciferase assays revealed that overexpression of miR-542-5p reduced the expression of p21-activated kinase 1 (PAK1), and subsequently inhibited the activation of MAPK-related signalling pathways, including extracellular signal-regulated kinase 1/2 (ERK1/2), JNK and P38MAPK. Finally, miR-542-5p overexpression reduced the release of IL-1β, TNF-α, ICAM-1 and other factors, thereby improving the severity of SAP-ALI [ 96 ]. In a study performed by Wang et al, miR-21-3p was found that to be highly expressed in acute haemorrhagic necrotizing pancreatitis (AHNP), and its overexpression activated the transient receptor potential (TRP) signalling pathway; promoted the release of serum amylase, lipase and inflammatory factors; inhibited lung oxygenation; and aggravated pancreatic and lung damage.…”

Signal Pathways and Markers Involved in Acute Lung Injury Induced by Acute Pancreatitis

“…AT-Lipoxin A4 inhibits the p-JNK/MAPK and p-ERK/MAPK pathways [ 32 ]. Substance P (SP)/neurokinin-1 receptor (NK1R) may regulate pancreatitis leukotriene B4 (LTB4) production via the MAPK signaling pathway, and LTB4 may regulate neutrophil reverse transendothelial migration (rTEM) in AP, which further promotes AP-ALI [ 32 , 33 ]. Upregulation of microRNA-542-5p downregulates the expression of P21-associated kinase 1 (PAK1), and downregulation of PAK1 may contribute to inhibition of the MAPK signaling pathway [ 33 ].…”

“…Substance P (SP)/neurokinin-1 receptor (NK1R) may regulate pancreatitis leukotriene B4 (LTB4) production via the MAPK signaling pathway, and LTB4 may regulate neutrophil reverse transendothelial migration (rTEM) in AP, which further promotes AP-ALI [ 32 , 33 ]. Upregulation of microRNA-542-5p downregulates the expression of P21-associated kinase 1 (PAK1), and downregulation of PAK1 may contribute to inhibition of the MAPK signaling pathway [ 33 ]. Lipoprotein A4 (LXA4) blocks ALI by inhibiting the inflammatory pathways of NF- κ B and p38MAPK and by upregulating cytoprotective heme oxygenase-1 (HO-1) [ 34 ] ( Figure 3 ).…”