@article {OhkouchiP748, author = {Shinya Ohkouchi and Manabu Ono and Masakazu Ichinose}, title = {The enhancement of Stanniocalcin-1 (STC1) secretion increases the ability of mesenchymal stem cells (MSCs) to reduce bleomycin-induced lung fibrosis in a mouse model through inhibition of endoplasmic reticulum stress (ER-stress)/TGFβ1 pathway}, volume = {44}, number = {Suppl 58}, elocation-id = {P748}, year = {2014}, publisher = {European Respiratory Society}, abstract = {RATIONALE: Mesenchymal-stem-cells (MSCs) ameliorate fibrosis in bleomycin-induced-lung-injury model. MSCs diminish oxidative stress and rescue alveolar-epitelial-cells (AECs) from apoptosis through secretion of Stanniocalcin-1 (STC1). We hypothesized STC1 contributes to abilities of MSCs ameliorating bleomycin-induced-lung-injury via the protection from oxidative-stress and anti-fibrotic effects by diminishing the endoplasmic-reticulum (ER) stress.METHODS: C57BL/6 mice were intratracheally injected with bleomycin. After 24 hrs, human MSCs transfected with STC1 plasmid or control were injected into the tail vein.14 days after instillation, pathologic findings were evaluated with immunohistochemistry of TGF-β1 and the ER stress marker, BiP. Anti-fibrotic effects were evaluated by measuring total lung collagen. Oxidative stress was evaluated by 8-Hydroxydeoxyguanosine (8-OHdG) staining.RESULTS: STC1-overexpressing MSCs enhanced the abilities to ameliorate bleomycin-induced-lung-fibrosis through the reduction of collagen accumulation, oxidative stress and ER-stress on the dependency of STC1 secretion. STC1 secretion in MSCs was controlled by mTOR induced by TGF-β1 in MSCs microenvironments.CONCLUSIONS: These results suggest that STC1 enhanced the ability of MSCs to ameliorate lung fibrosis via the inhibition of ROS production, reduction of ER stress and decrease of TGF-β1.}, issn = {0903-1936}, URL = {https://erj.ersjournals.com/content/44/Suppl_58/P748}, eprint = {https://erj.ersjournals.com/content}, journal = {European Respiratory Journal} }