The Research about the Regulation of Mesenchymal Stem Cell Exosomes on Sodium Transport of Lung Epithelium

This study discussed the regulation of BMSC-exo (bone mesenchymal stem cell-exosome) derived from mouse on alveolar epithelial sodium transport disorders caused by lung injury. The exosomes from the conditioned medium of BMSCs were isolated and their morphology, structure and size were identified by transmission electron microscopy. The cultured H441 cells, the classical lung epithelial cell line, were treated with lipopolysaccharide or exosomes, respectively. The expression of sodium ion channels at mRNA and protein levels in H441 cells separately was detected by qRT-PCR and Western blot. The results of this study showed that the protein expression levels of α-, γ-ENaC in the group combined exosomes and LPS were significantly increased compared with the LPS-treated group. Besides, the mRNA expression levels of the α-, β-, and γ-subunits were also significantly increased. In addition, our results also showed that the expression of miR-199a-3p in LPS-treated H441 cells was significantly decreased. Compared with the LPS group, miR-199a-3p expression was significantly increased in the exosome treatment group at 20 μg/mL. Compared with negative control group, the expression levels of α- and γ-ENac in H441 cells transfected with miR-199a-3p mimic were significantly increased, while those of miR-199a-3p inhibitor group were significantly decreased compared with inhibitor negative control group. The prediction of the website showed that mTOR (mammalian target of rapamycin) was the direct target of miR-199a-3p. mTOR protein expression of the group transfected with miR-199a-3p mimic was significantly lower than the negative control group, while mTOR expression of the group transfected with miR-199a-3p inhibitor was significantly increased compared with the inhibitor negative control group. The above results suggest that BMSC-exo may participate in the mTOR pathway through miR-199a-3p to regulate the expression of sodium ion channels in alveolar epithelial cells to promote the ion transport in pulmonary epithelium, which may further improve the clearance of pulmonary fluid under pathological conditions and participate in the treatment of clinical acute lung injury and other related edema lung diseases.

CSTR: 32200.14.cjcb.2021.02.0012