PT  - JOURNAL ARTICLE
AU  - Xuefeng Xu
AU  - Xuan Wan
AU  - Jing Geng
AU  - Fi Li
AU  - Chen Wang
AU  - Huaping Dai
TI  - In vitro profibrotic effects of rapamycin on basal or TGF-β1 induced primary human lung fibroblast: ECM production and turnover, migration and differentiation
DP  - 2012 Sep 01
TA  - European Respiratory Journal
PG  - P3628
VI  - 40
IP  - Suppl 56
4099  - http://erj.ersjournals.com/content/40/Suppl_56/P3628.short
4100  - http://erj.ersjournals.com/content/40/Suppl_56/P3628.full
SO  - Eur Respir J2012 Sep 01; 40
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.