Conditioned media from BMSC attenuate endoplasmic reticulum stress in alveolar epithelial cells by HGF invitro

Introduction Idiopathic Pulmonary Fibrosis (IPF) is a chronic progressive lung disorder of unknown etiology. Evidence of endoplasmic reticulum (ER) stress has been found in IPF patients. In this study we investigate possible effects of Bone Marrow Stromal Cell conditioned media (BMSC-cm) on ER stress and wound healing in alveolar epithelial cells line (AEC) and IPF primary cells. Methods ER stress was induced by growing A549 cells in Tunicamycin (TN) 3µg/ml for 24 h. Continuous the cells were treated with BMSC-cm or control media for 24h. qRT PCR was performed for analysis of ER stress markers: Grp78, XBP1 and CHOP and the wounds were measured at 0h, 24h. IPF primary cells were treated with BMSC-cm or control media and analyzed. BMSC-cm was treated by blocking HGF antibody and the analysis was repeated. Results Gene expression level of Grp78 in A549 was reduced after BMSC-cm treatment at 24h compared to controls (3.03±0.36 vs 4.86±0.76). Similarly, the spliced variant of XBP1 (4.07±0.41vs 5.42±0.51) and CHOP levels (10.13±1.39 vs 1.74±1.07) were diminished after BMSC-cm compared to controls. Furthermore, the percentage of alveolar wound repair was increased in presence of BMSC-cm in ER stressed cells as compared to controls at 24h (48.50%±5.1 vs 20.34%±2.51). In primary IPF cells similar reduction in gene expression of ER stress markers was observed. Conclusions BMSC-cm increases alveolar epithelial wound healing, possibly by reducing ER stress in AEC. Since ER stress predisposes to AEC dysfunction and subsequent lung fibrosis, our study emphasize that ER stress inhibition may serve as important therapeutic target in IPF, perhaps by BMSC-cm and probably by rHGF involved.