Nebulized MSC exosomes promote the transdifferentiation of transitional state cells against acute lung injury through STAT3/Krt8/AQP5 axis

Abstract

The transdifferentiation of alveolar epithelial type II cells (AECIIs) to alveolar epithelial type I cells (AECIs) plays an important role in the epithelial repair in acute lung injury (ALI). Although transitional state cells have been reported to regenerate the alveolar epithelium surface and promote a repair process, the treatment of ALI based on transitional state cells has not been suggested.

Here, we demonstrate that nebulized mesenchymal stem cell exosomes (MSC exosomes) can be used for ALI and MSC exosomes have the ability to promote the differentiation of transitional state cells into AECIs by regulating the STAT3/Krt8/AQP5 axis. In the in vivo study, immunohistochemistry and immunofluorescence staining results showed that MSC exosomes could reduce the expression of transitional state cells and promote transdifferentiation of AECIIs. In the in vitro study, western blotting (WB) results showed that MSC exosomes downregulated signal transducer and activator of transcription 3 (STAT3) phosphorylation and the expression of transitional state cell specific keratin 8 (Krt8), and upregulated the expression of AECIs specific aquaporin 5 (AQP5). The results indicate that MSC exosomes inhibit STAT3 phosphorylation through STAT3/Krt8/AQP5 axis, promote the transdifferentiation of transitional state cells to AECIs and accelerate the regeneration of alveolar epithelium after LPS-induced lung injury. Regulating transitional state cells to alleviate ALI is suggested for the first time.