A TSP-1 functional fragment inhibits activation of latent transforming growth factor-beta 1 derived from rat alveolar macrophage after bleomycin treatment

作者：Chen Ying; Wang Xin; Weng Dong; Tao Shasha; Lv Lina; Chen Jie^*

来源：Experimental and Toxicologic Pathology, 2009, 61(1): 67-73.

DOI：10.1016/j.etp.2008.06.007

• Thrombospondin-1
• Latent transforming growth factor-beta 1
• Activation
• Bleomycin-induced lung injury
• Alveolar macrophage

The antineoplastic antibiotic. bleomycin. is known to Induce a well-recognized model of lung fibrosis. Active transformation growth factor-beta 1 (TGF-beta 1) plays a key role in lung fibrosis induced by belomycin. TSP-1 (thrombospondin-1) being critical to the activation of L (latent)-TGF-beta 1 by virtue of an association of the TSP-1/L-TGF-beta 1 complex with CD36. involving the sequence CSVTCG of the TSP-1 functional fragruent. To observe the inhibitory effects of TSP-1 functional fragments, critical for CD36 binding, on the activation of L-TGF-beta 1, we isolated alveolar macrophages from Wistar rat lungs 7 days after bleomycin administration (5 mg/kg body weight) and Cultured the cells with or without TSP-1 functional or control fragments. We observed a cell surface association of TGF-beta 1 with CD36 by immunofluorescence and quantified the active and total TGF-beta 1 by ELISA. The co-localization of CD36 with TGF-beta 1, shown by a yellow fluorescence deriving from a mixture of the green and red of the two components. for the TSP-1 functional fragment groups was clearly less than that of the TSP-1 control fragment groups. The quantities and the percentages of active TGF-beta 1 in the TSP-1 Functional fragment groups were lower than those in the TSP-1 control fragment groups (P<0.05 or P<0.01). These findings suggest that TSP-1 functional fragments could Inhibit the activation of L-TGF-beta 1 secreted by activated alveolar macrophages through blocking the binding of TSP-1 to CD36.

• 出版日期2009-1
• 单位中国医科大学