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

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 in vitro lipopolysaccharide- (LPS-) established alveolar epithelial cell inflammation model and an in vivo 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-1α can regulate the expression of SLUG, which in turn can regulate the key gene E-Cadherin 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-1α/SLUG signaling pathway in ARDS, and thereby alleviates pulmonary fibrosis.

SnRNA-Seq analysis reveals ten hub genes associated with alveolar epithelial cell injury during pulmonary acute respiratory distress syndrome

“…At the same time, we found that ITGA3 is closely related to EMT. On the one hand, several studies have found that EMT plays an important role in ARDS [ 15 , 16 ], on the other hand, ITGA3 has been confirmed to participate in the development process of tumors by participating in EMT in a variety of tumors [ 17 , 18 ]. We believe that it is meaningful to conduct subsequent experiments to specifically explore whether ITGA3 can play a role in the occurrence and development of ARDSp by participating in EMT.…”

Microvesicles derived from mesenchymal stem cells inhibit ARDS pulmonary fibrosis partly through HGF

“…Pulmonary brosis is highly associated with poor prognostic outcomes of ARDS patients [16][17][18]. Currently, there are no effective measures for anti-pulmonary brosis treatment [19][20]. The MSC-MVs have anti-pulmonary brosis effects, however, their speci c effects and mechanisms on ARDS pulmonary brosis have not been fully established [21].…”