RT Journal Article
SR Electronic
T1 In vitro profibrotic effects of rapamycin on basal or TGF-β1 induced primary human lung fibroblast: ECM production and turnover, migration and differentiation
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P3628
VO 40
IS Suppl 56
A1 Xuefeng Xu
A1 Xuan Wan
A1 Jing Geng
A1 Fi Li
A1 Chen Wang
A1 Huaping Dai
YR 2012
UL http://erj.ersjournals.com/content/40/Suppl_56/P3628.abstract
AB Introduction or background: Rapamycin (Rapa) is a multifunctional agent with unique properties such as anti-proliferation and fibrogenesis. However, the underlying mechanisms of Rapa's modulatory effects on fibrotic disorders still remain poorly understood. Recent remarks about the final and real modulatory effects of Rapa on fibrogenesis also seem rather controversial.Aims and objectives: We addressed the question whether Rapa exerts its possible modulatory activity directly on extracellular matrix deposition and metabolism, differentiation and migration of primary normal or fibrotic human lung fibroblast (HLFs) in vitro.Methods: Fibroblasts were derived from lung tissue of idiopathic pulmonary fibrosis(IPF) patients and patients who suffered from primary spontaneous pneumothorax. Real time RT PCR was used for the assay of mRNA level of profibrotic cytokines in fibroblasts. Wound healing and migration assay was used for the mobility analysis of fibroblasts.Results: We demonstrated that Rapa strongly amplifies the increase in basal or TGF-β1-induced fibronectin (FN), connective tissue growth factor (CTGF), TGF-β1, α-smooth muscle actin (SMA), tissue inhibitor of matrix metalloproteinase (TIMP)-1/ plasminogen activator inhibitor (PAI-1) mRNA levels in normal or fibrotic HLFs. These positive functions of Rapa are in a Smad-independent way. Wound healing and migration assay showed that Rapa could not affect the mobility of HLFs.Conclusions: These experiments demonstrate that Rapa positively regulates various gene expressions of HLFs. We suggest another evidence that Rapa may exert a profibrotic effects in vitro.