转化生长因子-β信号促进由schistosoma mansoni引起的肺高血压
Brian B Graham1, Jacob Chabon, Liya Gebreab
1Program in Translational Lung Research, Division of Pulmonary Sciences and Critical Care Medicine (B.B.G., J.C., L.G., J.P., E.D., L.D., T.T., L.S., N.D., R.W.V.) and Department of Pathology (X.-J.W.), Anschutz Medical Campus, Aurora, CO; Pulmonary Vascular Research Institute (B.B.G., A.B., H.C.C., G.B., R.M.T.); Memorial S. Jose Hospital, Universidade de Pernambuco in Recife, Recife, Brazil (A.B.); Division of Cardiology, University of Pittsburgh, Pittsburgh, PA (H.C.C.); School of Pharmacy, University of Kent, Kent, UK (G.B.); and Immunopathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (T.A.W.).
schistosomiasis引起的肺动脉高血压涉及转化生长因子-β (TGF-β) 信号传输. 阻断TGF-β通路可以保护小鼠免受疾病的发展,这表明它是一种治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 心血管研究研究心血管研究
- 寄生虫学的寄生虫学
背景情况:
- 来自杆菌病的肺动脉高血压 (PAH) 是一个全球性健康问题,其原因尚不清楚.
- 转化生长因子-β (TGF-β) 信号被假定是由于Th2炎症引起的PAH病原体的关键.
研究的目的:
- 为了研究TGF-β信号传递在与杆菌病相关的肺动脉高血压中的作用.
- 探索这种情况的潜在治疗点.
主要方法:
- 通过 Schistosoma mansoni 蛋对小鼠进行敏感化和挑战,以模拟这种疾病.
- 使用了对TGF-β连接体和受体的药理学阻断.
- 缺乏Smad3基因的小鼠被用来评估TGF-β通路的依赖性.
- 测量了中白素-4和中白素-13的水平.
主要成果:
- 胞卵挑战诱导的PAH,其特征是右心室缩压的增加,肺动脉介质的加厚,以及右心室缩.
- 罗基纳酶依赖的血管收缩显著导致血压升高.
- 阻断TGF-β信号传递或使用Smad3缺乏的小鼠,保护它们免受PAH的发展.
- 阻断TGF-β可以降低介质蛋白-4和介质蛋白-13的水平.
- 人类肺部样本显示了TGF-β信号在PAH中的证据.
结论:
- 规范性TGF-β信号传递对于实验性Schistosoma mansoni诱导的肺血管疾病至关重要.
- 准TGF-β信号传递可能是治疗杆菌病相关的PAH的可行策略.
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