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Poly r(C) binding protein 1‐mediated regulation of microRNA expression underlies post‐sevoflurane amelioration of acute lung injury in rats

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Journal of Cellular Physiology

Published online on

Abstract

Acute lung injury (ALI) presents a pervasive health burden due to the high morbidity and mortality associated with it. Volatile anesthetics like sevoflurane has been previously shown to have organ‐protective effect, both in the context of normal physiological function in liver, and during LPS‐induced ALI. Sevoflurane was shown to exert lung protective effect during LPS‐induced ALI by modulating expression level of microRNAs (miRNAs), specifically miR‐155. The objective of the current study was to define the underlying mechanism by which sevoflurane alters miRNA expression levels. Lung injury caused by LPS and its amelioration post sevoflurane administration was first confirmed. Expression levels of different miRNA and messenger RNAs (mRNAs) encoding inflammatory cytokines were measured in a rat model of lipopolysaccharide (LPS)‐induced ALI, which were subsequently treated with either sevoflurane or vehicle control. Host of miRNAs and messenger RNAs encoding pro‐inflammatory cytokines are overexpressed during LPS‐induced ALI, which are reversed following sevoflurane administration. Mass spectrometry analysis revealed that the RNA‐binding protein, poly r(C) binding protein 1 (PCBP1) expression is induced in ALI and is repressed following sevoflurane treatment. RNA immunoprecipitation experiments revealed that PCBP1 expression dictates the altered miRNA expression and sevoflurane altered miRNA expression by suppressing PCBP1 expression. Our study thus elucidates a unique mechanism of lung protective effect of sevoflurane mediated by suppression of expression of a RNA‐binding protein that potentiates expression of pro‐inflammatory miRNAs. Our study thus elucidates a unique mechanism of lung protective effect of sevoflurane mediated by suppression of expression of a RNA‐binding protein that potentiates expression of pro‐inflammatory miRNAs.