MicroRNA-377-3p released by mesenchymal stem cell exosomes ameliorates lipopolysaccharide-induced acute lung injury by targeting RPTOR to induce autophagy

Abstract

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the severe lung damage and respiratory failure without effective therapy. However, there was a lack of understanding of the mechanism by which exosomes regulate autophagy during ALI/ARDS. Here, we found lipopolysaccharide (LPS) significantly increased inflammatory factors, administration of exosomes released by human umbilical cord mesenchymal stem cells (hucMSCs) successfully improved lung morphometry. Further studies showed that miR-377-3p in the exosomes played a pivotal role in regulating autophagy, leading to protect LPS induced ALI. Compared to exosomes released by human fetal lung fibroblast cells (HFL-1), hucMSCs-exosomes overexpressing miR-377-3p more effectively suppressed the bronchoalveolar lavage (BALF) and inflammatory factors and induced autophagy, causing recoveration of ALI. Administration of miR-377-3p expressing hucMSCs-exosomes or its target regulatory-associated protein of mTOR (RPTOR) knockdown significantly reduced ALI. In summary, miR-377-3p released by hucMSCs-exosomes ameliorated Lipopolysaccharide-induced acute lung injury by targeting RPTOR to induce autophagy in vivo and in vitro.

Heat Shock Preconditioning Mesenchymal Stem Cells Attenuate Acute Lung Injury via Reducing NLRP3 Inflammasome Activation in Macrophages

“…Our previous researches provided reliable results on the bene cial effects of MSCs on improving liver ischemia/reperfusion injury (IRI) in vivo and in vitro [10,11]. In addition, our and other several studies have also shown that MSCs could alleviate lipopolysaccharide (LPS)-induced ALI via their well-de ned roles in immunomodulation and differentiation into multiple different cell types, including adipocytes, osteoblasts and lung-related cell types [12][13][14][15][16][17].…”

Extracellular Vesicles for the Treatment of Radiation Injuries

“…This is followed by an increase in inflammatory cytokines (TNF-α and IL-6), natural killer (NK) cells, Mɸ polarization, edema, and lung perfusion, eventually activating fibroblasts and myofibroblast differentiation to fibrosis in the irradiated lung ( Kabarriti et al, 2020 ). MSCs derived from the umbilical cord ( Wei et al, 2020 ), bone marrow ( Lee et al, 2012 ), and adipose tissue ( Dong et al, 2015 ) were reported to be attenuating various models of lung injury.…”

Knockdown of hsa_circ_0001275 reverses dexamethasone-induced osteoblast growth inhibition via mediation of miR-377/CDKN1B axis

“…Similar function was noted between CDKN1B and PTEN. On the other hand, more mRNAs can be targeted by miR-377 [42,43]. Zhou W et al found NR6A1 was targeted by miR-377 in gastric cancer [43], and miR-377 could alleviate myocardial injury induced by Hypoxia/Reoxygenation via downregulating LILRB2 expression [31].…”