Abstract:Objective To investigate whether bone marrow mesenchymal stem cell（BMSC）-derived exosomes（Exo）can inhibit pulmonary fibrosis by regulating epithelial-mesenchymal transition（EMT）via the transglutaminase（TG）2/nuclear factor κB（NF-κB）pathway. Methods SPF-grade male SD rats were selected, and BMSCs and their derived Exo were isolated, cultured and identified；human alveolar epithelial A549 cells were stimulated with transforming growth factor（TGF）-β1 to establish a pulmonary fibrosis（PF）model. A549 cells with TGM2 knockdown（TG2-）, TGM2 overexpression（TG2+）and empty vector（TG2--con or TG2+-con）were constructed, and were subjected to no treatment（NC group）, TGF-β1 treatment（PF group）, and Exo treatment（Exo group）, respectively. Western blot was used to detect the protein expression of E-cadherin, Vimentin, TG2 and NF-κB. Results Compared with the NC group, the PF group showed significantly decreased E-cadherin expression, while the expression levels of Vimentin and TG2 protein were significantly increased（P＜0.05）. Compared with the PF group, the Exo group showed increased E-cadherin expression and decreased expression levels of Vimentin and TG2 protein（P＜0.05）. TGM2 over expression upregulated NF-κB, and TGM2 knockdown downregulated NF-κB（P＜0.05）.After Exo intervention, E-cadherin increased in the TG2- group, TG2+ group, TG2--con group and TG2+-con group, while Vimentin, TG2 and NF-κB were all significantly decreased（P＜0.05）.Conclusion TGM2 is a key target of BMSC-Exo in regulating EMT. BMSC-Exo can regulate the EMT process by inhibiting the TG2/NF-κB pathway, thereby exerting an inhibitory effect on pulmonary fibrosis.