Combined treatment with mesenchymal stem cells and ROCK inhibitor Y-27632 ameliorates PM2.5-induced lung injury

Particulate matter 2.5 mu m (PM2.5) can directly enter the human respiratory tract and cause damage to lungs. Mesenchymal stem cells (MSCs) transplantation has emerged as a promising therapeutic strategy for ameliorating lung injury. Nonetheless, the lineage fate of recruited MSCs in the lung can be impacted by Rho-associated protein kinase 1 (ROCK) signaling. The current study investigated whether a combined treatment of MSCs with ROCK inhibitor Y-27632 offers enhanced therapeutic efficacy in addressing PM2.5-induced lung injury. The combined therapeutic efficacy was analyzed by wound healing assay, oxidative response and inflammatory factors in PM2.5-treated A549 cells. Besides, the combined MSCs and Y-27632 therapy was also analyzed by lung pathology, EMT response and inflammatory factors in PM2.5-treated mice. Combined MSCs and Y-27632 treatment more effectively restored wound healing ability and attenuated oxidative stress and inflammatory response in PM2.5-injured A549 cells than MSCs monotherapy. Immunohistochemical analysis result demonstrated that PM2.5 exposure altered markers related to epithelial-to-mesenchymal transition (EMT), such as E-cadherin, alpha-SMA and vimentin in lung tissue. Both MSCs monotherapy and combined MSCs and Y-27632 therapy restored lung injury by reducing lung pathology, oxidative stress, inflammatory response, and EMT process by inhibiting beta-catenin pathway. However, the combined treatment proved more efficacious in mitigating PM2.5-induced lung injury. Although MSCs alleviated PM2.5-induced lung injury, the combined therapeutic efficacy of MSCs and Y-27632 offered a better treatment effect. This study offers valuable insights into the mechanisms of lung injury induced by PM2.5 and potential interventional treatments.