Inositol Alleviates Pulmonary Fibrosis by Promoting Autophagy Via Inhibiting the HIF-1-SLUG Axis in Acute Respiratory Distress Syndrome

Overview

Journal Oxid Med Cell Longev

Publisher Wiley

Specialties Cell Biology
Endocrinology

Date 2023 Jan 2

PMID 36589681

Authors

Yufeng Liang

Yingyi Xu

Bingtai Lu

Yuanming Huang

Shuman Xu

Junjie Xie

Ming Liu

Di Che

Liuheyi Ma

Jianping Tao

Jie Hong

Jianhui Zhang

Xun Situ

XinXu Ou

Lihe Chen

Yang Li

Lihong Zhang

Zhiyuan Wu

Affiliations

Soon will be listed here.

Abstract

The effective remission of acute respiratory distress syndrome- (ARDS-) caused pulmonary fibrosis determines the recovery of lung function. Inositol can relieve lung injuries induced by ARDS. However, the mechanism of myo-inositol in the development of ARDS is unclear, which limits its use in the clinic. We explored the role and mechanism of myo-inositol in the development of ARDS by using an lipopolysaccharide- (LPS-) established alveolar epithelial cell inflammation model and an ARDS mouse model. Our results showed that inositol can alleviate the progression of pulmonary fibrosis. More significantly, we found that inositol can induce autophagy to inhibit the progression pulmonary fibrosis caused by ARDS. In order to explore the core regulators of ARDS affected by inositol, mRNA-seq sequencing was performed. Those results showed that transcription factor HIF-1 can regulate the expression of SLUG, which in turn can regulate the key gene involved in cell epithelial-mesenchymal transition (EMT) as well as N-cadherin expression, and both were regulated by inositol. Our results suggest that inositol activates autophagy to inhibit EMT progression induced by the HIF-1/SLUG signaling pathway in ARDS, and thereby alleviates pulmonary fibrosis.

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