Decorin and IL-10 co-overexpression in BMDMSCs attenuates pulmonary fibrosis – an experimental study

Background: This study investigated whether the double overexpression of decorin and IL-10 in human bone marrow-derived mesenchymal stem cells [HBMDMSCs DO (DEC/IL-10) ] can protect against bleomycin (BLM)-induced pulmonary fibrosis (PF) in mice. Methods: L2 and NR8383 cells were treated with BLM (0–2.5 μg/mL). In vivo , animals were assigned to four groups: Group 1 – sham control (SC); Group 2 – PF; Group 3 – PF + HBMDMSCs; Group 4 – PF + HBMDMSCs DO (DEC/IL-10) . Results: BLM, at its IC 50 , significantly reduced the viability of L2 and NR8383 cells while increasing early and late apoptosis and TGF-β expression ( P < 0.001). BLM treatment in L2 cells induced oxidative stress (mitochondrial ROS, NOXs/p22 phox ), cell-stress signaling (MAPKs), and epithelial–mesenchymal transition (EMT) biomarkers, which were reversed by decorin, HBMDMSCs, decorin-overexpressing HBMDMSCs, or p22 phox silencing ( P < 0.001). Decorin silencing in L2 and CG1629 cells upregulated EMT and cell-stress markers, effects reversed by decorin treatment, decorin overexpression, or MSC DO (DEC/IL-10) ( P < 0.001). In BLM-induced PF mice, SaO 2 was highest in Group 1, lowest in Group 2, and higher in Group 4 than Group 3, while lung injury, fibrosis, right-ventricular pressure, and inflammatory cells showed the opposite trend ( P < 0.0001). Lung expression of EMT/proliferation (c-Myc, Cyclin D/E, Wnt/β-catenin), oxidative stress (p22 phox , OxyBlot), and fibrosis (TGF-β, p-Smad3) proteins mirrored lung injury scores ( P < 0.0001). Conclusion: HBMDMSCs DO (DEC/IL-10) treatment effectively protected the lungs from BLM-induced PF in rodents.