Aims: Acute lung injury (ALI) is a clinical syndrome with high morbidity and mortality, and severe pulmonary edema is one of the characteristics of ALI. Epithelial sodium channel (ENaC) located on the apical side of alveolar type 2 epithelial (AT2) cells is the primary rate limiting segments in alveolar fluid clearance. Many preclinical studies have revealed that mesenchymal stem cells (MSCs) based therapy has great therapeutic potential for ALI, while the role of ENaC in this process is rarely known.
Methods: We studied the effects of bone marrow-derived MSCs (BMSCs) on the protein/mRNA expression and activity of ENaC in primary mouse AT2 and H441 cells by co-culture with them, respectively. Moreover, the changes of miRNA-130b in AT2 cells were detected by qRT-PCR, and we studied the involvement of phosphatase and tensin homolog deleted on chromosome ten (PTEN) in miRNA-130b regulated ENaC.
Results: Our results demonstrated that BMSCs could increase the expression of miRNA-130b, which showed adverse effects on the protein expression of α/γ-ENaC and PTEN in AT2 cells. SiRNA-mediated downregulation of PTEN could increase the protein expression of α/γ-ENaC in AT2 cells, supporting PTEN as a negative regulator of ENaC.
Conclusion: In summary, miRNA-130b in BMSCs can enhance ENaC at least partially by targeting PTEN, which may provide a promising new direction for therapeutic strategy in ALI.
