The Effect Of Transforming Growth Factor β1 On Thy-1, Caveolin-1 And Its Implications In Pulmonary Fibrosis

PrefaceCaveolin-1 is one of the most important member of a family of membrane proteins that are the major coating proteins of caveolae which are 50～100nm flask-shaped invaginations that represent a morphologically identifiable subset of lipid raft.Recent findings indicate that there is a close relationship between caveolin-1 and pulmonary fibrosis.Fibroblasts which are major biosynthetic cells in pulmonary fibrosis were shown in recent studies that they are not homogeneous subsets.Based on cell membrane glycoprotein thy-1,fibroblasts are divided into two characteristically subsets ie,thy-1+ subset and thy-1- subset.However,expression of caveolin-1 in the two subsets was not explored currently.This article also sought to determine the expression of caveolin-1 in NIH3T3 fibroblasts under the influence of profibroblastic factor TGF-beta1.Further,we also replicated rat fibrosis model by bleomycin instillation intratracheally.And,the caveolin-1 level was also investigated.Materials and Methods一,Materials1,NIH3T3 cell line2,TGF-β13,Caveolin-1 antibody4,Thy-1 antibody5,DMEM culture medium6,Fetal bovine serum 7,wistar rats二,Methods1,Flow cytometry2,fluorescent activated cell sorting3,immunoblotting4,immunohistochemistryResults1,TGF-βlean decrease the level of caveolin-1 in fibroblast in a time and dose dependent manner.2,TGF-β1 has little influence on the expression of thy-1 in NIH3T3 fibroblast.3,Thy-1+ fibroblast subset has a higher baseline level of caveolin-1 than thy-1-subsets.4,The level of caveolin-1 decreases as fibrosis progress.DiscussionIdiopathic pulmonary fibrosis is a progressive and lethal disease,whose main biosynthetic cell is fibroblasts.Based on cell membrane glycoprotein thy-1,fibroblasts can be divided into two characteristically subsets.caveolin-1,the most important component of eaveolae,plays a role in multiple systems and diseases.To our knowledge,we are the first to explore the level of caveolin-1 of the two subsets and find thy-1- subset has a higher baseline level.We presume that the decrease level of cavolin-1 was responsible for the high responsibility of thy-1- fibroblast to profibroblastic factors.So far bleomycin is the standard agent for induction of experimental pulmonary fibrosis in animals.In this experiment we also replicated this model in wistar rats and investigated the expression of caveolin-1.Further research on caveolin-1 may provide a new way for the pathogenesis and therapy of idiopathic pulmonary fibrosis.Conclusion The expression of caveolin-1 differ in thy-1+ and thy-1- subsets,and the decrease level of cavolin-1 may be responsible for the high responsibility of thy-1- fibroblast to profibroblastic factors.The different positive rate of thy-1 in different cell types and distinct response to profibroblastic factors may be another proof of the fibroblast heterogeneity.Caveolin-2 was involved in the progress of pulmonary fibrosis, Treatment approaches that augment caveolin-1 bioavailability may help store normal alveolar epithelial repair and regeneration and slow the progression of fibrosis.