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Dasatinib attenuated bleomycin-induced pulmonary fibrosis in mice

机译:达沙替尼减轻博来霉素诱导的小鼠肺纤维化

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摘要

Anti-fibrotic effect of dasatinib, a platelet-derived growth factor receptor (PDGFR) and Src-kinase inhibitor, was tested on pulmonary fibrosis (PF). Adult mice were divided into four groups: mice dissected 21d after the bleomycin (BLM) instillation (0.08mg/kg in 200 mu l) (I) and their controls (II), and mice treated with dasatinib (8mg/kg in 100 mu l, gavage) for one week 14d after BLM instillation and dissected 21d after instillation (III) and their controls (IV). The fibrosis score and the levels of fibrotic markers were analyzed in lungs. BLM treatment-induced cell proliferation and increased the levels of collagen-1, alpha smooth muscle actin, phospho (p)-PDGFR-alpha, p-Src, p-extracellular signal-regulated kinases1/2 and p-cytoplasmic-Abelson-kinase (c-Abl) in lungs, and down-regulated PTEN expression. Dasatinib reversed these alterations in the fibrotic lung. Dasatinib limited myofibroblast activation and collagen-1 accumulation by the inhibition of PDGFR-alpha, and Src and c-Abl activations. In conclusion, dasatinib may be a novel tyrosine and Src-kinase inhibitor for PF regression in mice.
机译:测试了dasatinib(一种血小板衍生的生长因子受体(PDGFR)和Src激酶抑制剂)对肺纤维化(PF)的抗纤维化作用。将成年小鼠分为四组:博莱霉素(BLM)滴注后第21天(200μl,0.08mg / kg)(I)和其对照组(II);和达沙替尼(8mg / kg,100μl)处理的小鼠BLM滴注后第14天(l,管饲)1周,滴注后(III)及其对照组(IV)解剖21d。在肺中分析纤维化得分和纤维化标记物的水平。 BLM治疗诱导的细胞增殖并增加了胶原蛋白1,α平滑肌肌动蛋白,磷酸(p)-PDGFR-α,p-Src,p-细胞外信号调节激酶1/2和p-胞质Abelson激酶的水平(c-Abl)在肺中,并下调PTEN表达。达沙替尼逆转了纤维化肺中的这些改变。达沙替尼通过抑制PDGFR-α以及Src和c-Abl激活来限制成肌纤维细胞的激活和1型胶原的积累。总之,达沙替尼可能是一种新型的酪氨酸和Src激酶抑制剂,可减轻小鼠的PF。

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