Effect of A Blocking Peptide for Activation of Latent TGF-β In Prevention of Pulmonaiy Fibrosis.

转化生长因子β-1是肾、肝、肺纤维化的重要细胞因子。凝血酶敏感蛋白-1与潜伏期转化生长因子-β复合体中的潜伏期相关肽(LAP)相互作用，调节潜伏期转化生长因子-β1的激活。位于LAP氨基末端的亮氨酸-丝氨酸-赖氨酸-亮氨酸(Leu-Ser-Lys-Leu，LSKL)可竞争性抑制凝血酶敏感蛋白介导的潜伏性转化生长因子-β1的激活。LSKL组12只，生理盐水组10只。每天持续吸入，持续2周。结果1)LSKIL组大鼠第14天体重与基线体重之比(1.29±0.40)高于生理盐水组(1.09±0.38)(P=O44)。2)LSKL组大鼠肺顺应性显著高于生理盐水组(1.98±0.46比1.36±0.16ml/cmH2O/kg，p&lt；0.05)。3)肺康口服液组大鼠肺组织羟脯氨酸含量明显低于生理盐水组(7.36±1.25vs 9.30±1.27μg/mg肺组织，p&lt；0.05)。THA多肽LSK1可能通过阻断转化生长因子-β-1的激活，为肺纤维化的治疗提供新的干预手段。

RATIONATE TGF-β1 is a critical cytokine of fibrosis in kidney, liver and lung. Thrombospondin-1 interacts with the latency-associated peptide (LAP) in the latent TGF-β complex and regulates activation of latent TGF-β1. A peptide Leu-Ser-Lys-Leu (LSKL), which represents in the amino terminus of LAP, competitively inhibits thrombospondin-mediated activation of latent TGF-β1. We hypothesized that a peptide LSKL may reduce fibrotic change in bleomycin-treated rat lungs.METHODS Four-week-old rats were administered LSKL or saline by nebulizer for 30 mm in chamber 2h before bleomycin (15mg/kg body weight) intratracheal injection. (LSKL group N=12, Saline group N=10). Inhalation was continued daily for 2 weeks. On 14 days, lung compliances were measured and lung tissues were used for hydroxyproline assay.RESULTS 1) Ratio of body weight of rats at day 14 to baseline were greater in LSKIL group than in saline group (1.29±0.40 vs 1.09±0.38 p=O 44). 2) Lung compliances were significantly higher in LSKL group than in saline group (1.98±0.46 vs. 1.36±0.16 ml/cmH_2O/kg, p<O.O5). 3) The hydroxyproline content in lung tissues were significantly lower in LSKL group than in saline group (7.36±1.25 vs 9.30±1.27μg/mg lung tissue, p<O.O5).CONCLUSION These results show that a peptide LSKL inhalation is effective to avoid deterioration of pulmonary function through prevention of progressive fibrosis in this model. Tha peptide LSKL may provide a novel therapeutic intervention in pulmonary fibrosis by blocking the activation of TGF-β1.