A TSP-1 synthetic peptide inhibits bleomycin-induced lung fibrosis in mice.
Bleomycin showed toxicity to lung and was recognized to induce a well model of lung fibrosis. Activated alveolar macrophages released increased amounts of transforming growth factor-beta1(TGF-beta1) in response to bleomycin-induced lung injury. Thrombospondin-1(TSP-1) was involved in the activation of latent TGF-beta1(L-TGF-beta1) through the association of the TSP-1/L-TGF-beta1 complex with the cell receptor of TSP-1, CD36. The antagonistic effects of the synthetic peptides were studied by the administration of TSP-1 (447-452) synthetic peptides to the mouse model. The hydroxyproline contents of the TSP-1-treated groups were significantly lower than those of other experimental groups. Inflammation, fibrotic degree and distribution of collagen fibers in the interstitial and alveolar in the TSP-1-treated groups were less than those of the other experimental groups. The expressions of collagen I and III in TSP-1-treated groups were significantly lower than in the other experimental groups. TSP-1 synthetic peptide reduced the tissue fibrotic pathologies and collagen accumulation in the model, resulting in the decreased severity of bleomycin-induced lung injury.
Chen
Ying
Y
China Medical University, Shenyang, PR China.
Wang
Xin
X
Weng
Dong
D
Tian
Lujia
L
Lv
Lina
L
Tao
Shasha
S
Chen
Jie
J
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D001761:Bleomycin / Q000633:toxicity*; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D006909:Hydroxyproline / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D010446:Peptide Fragments / Q000494:pharmacology*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D019700:Thrombospondin 1 / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D010446:Peptide Fragments; D019700:Thrombospondin 1; C494028:cysteinyl-seryl-valyl-threonyl-cysteinyl-glycine; D001761:Bleomycin; D003094:Collagen; D006909:Hydroxyproline