Abstract
Particulate matter 2.5 μm (PM(2.5)) 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 PM(2.5)-induced lung injury. The combined therapeutic efficacy was analyzed by wound healing assay, oxidative response and inflammatory factors in PM(2.5)-treated A549 cells. Besides, the combined MSCs and Y-27632 therapy was also analyzed by lung pathology, EMT response and inflammatory factors in PM(2.5)-treated mice. Combined MSCs and Y-27632 treatment more effectively restored wound healing ability and attenuated oxidative stress and inflammatory response in PM(2.5)-injured A549 cells than MSCs monotherapy. Immunohistochemical analysis result demonstrated that PM(2.5) exposure altered markers related to epithelial-to-mesenchymal transition (EMT), such as E-cadherin, α-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 β-catenin pathway. However, the combined treatment proved more efficacious in mitigating PM(2.5)-induced lung injury. Although MSCs alleviated PM(2.5)-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 PM(2.5) and potential interventional treatments.