心脏纤维化需要纤维细胞初级乳头
Elisa Villalobos1,2, Alfredo Criollo1,2,3, Gabriele G Schiattarella1
1Departments of Internal Medicine (Cardiology) (E.V., A.C., G.G.S., F.A., K.M.F., H.I.M., N.J., N.U.N.N., A.F., H.A.S., T.G.G., S.L., J.A.H.), University of Texas Southwestern Medical Center, Dallas.
Circulation
|March 2, 2019
概括
成人心脏纤维细胞中的初级乳毛对于心脏修复至关重要. 它们的缺失会损害纤维生成和重塑,将多囊病与心脏异常联系起来.
科学领域:
- 心血管生物学
- 细胞生物学
- 复原医学
背景情况:
- 在脊椎动物的发育过程中,
- 它们在成年心脏细胞中的存在和功能在很大程度上没有被描述.
- 多囊性病与纤毛细胞基因突变有关,有心血管方面的影响.
研究的目的:
- 在成人心脏细胞中识别初级乳毛.
- 在受伤后心脏重塑中研究初级乳毛的作用.
- 探索毛功能与遗传疾病的心血管表现之间的联系.
主要方法:
- 从小鼠和人类的心脏组织的组织学分析.
- 利用特定的抗体来识别主要的乳毛细胞,纤维细胞和心肌细胞.
- 使用损伤模型 (心肌梗塞,缺血/再输血) 和基因沉默技术 (肌纤维细胞中的PC1).
主要成果:
- 在小鼠,老鼠和人类心脏中的心脏纤维细胞中发现了主要的乳毛.
- 状纤维细胞集中在心肌损伤的区域.
- 纤维细胞中初级乳毛或PC1的消耗损害了TGF-β1 / SMAD3信号传递,ECM的产生和收缩功能,阻碍了心脏重塑.
结论:
- 成人心脏纤维细胞具有主要的乳毛,对于纤维化和心脏修复至关重要.
- 主性和PC1对于转化β-1生长因子信号,ECM合成和纤维细胞收缩性至关重要.
- 这些发现突显了主在病态心脏重塑中的作用,并表明它与多囊性病中的心血管问题有直接联系.
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