Type V Collagen in Scar Tissue Regulates the Size of Scar after Heart Injury.,Cell

当前位置： X-MOL 学术 › Cell › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Type V Collagen in Scar Tissue Regulates the Size of Scar after Heart Injury.
Cell ( IF 45.5 ) Pub Date : 2020-07-03 , DOI: 10.1016/j.cell.2020.06.030
Tomohiro Yokota ₁ , Jackie McCourt ₂ , Feiyang Ma ₃ , Shuxun Ren ₄ , Shen Li ₁ , Tae-Hyung Kim ₂ , Yerbol Z Kurmangaliyev ₅ , Rohollah Nasiri ₆ , Samad Ahadian ₇ , Thang Nguyen ₈ , Xing Haw Marvin Tan ₉ , Yonggang Zhou ₁ , Rimao Wu ₁ , Abraham Rodriguez ₁ , Whitaker Cohn ₁₀ , Yibin Wang ₄ , Julian Whitelegge ₁₀ , Sergey Ryazantsev ₁₁ , Ali Khademhosseini ₁₂ , Michael A Teitell ₁₃ , Pei-Yu Chiou ₉ , David E Birk ₁₄ , Amy C Rowat ₁₅ , Rachelle H Crosbie ₁₆ , Matteo Pellegrini ₃ , Marcus Seldin ₁₇ , Aldons J Lusis ₁₈ , Arjun Deb ₁

Affiliation

Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; UCLA Cardiovascular Theme, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; Department of Molecular, Cell and Developmental Biology, College of Letters and Sciences, University of California, Los Angeles, CA 90095, USA; Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA; California Nanosystems Institute, University of California, Los Angeles, CA 90095, USA.
Department of Integrative Biology and Physiology, University of California, CA 90095, USA.
Department of Molecular, Cell and Developmental Biology, College of Letters and Sciences, University of California, Los Angeles, CA 90095, USA; Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.
Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA; Department of Anesthesiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Department of Biological Chemistry, David Geffen School of Medicine, Los Angeles, CA 90095, USA.
California Nanosystems Institute, University of California, Los Angeles, CA 90095, USA; Department of Bioengineering, School of Engineering, University of California, Los Angeles, CA 90095, USA; Department of Mechanical Engineering, Sharif University of Technology, Tehran 11365-11155, Iran.
California Nanosystems Institute, University of California, Los Angeles, CA 90095, USA; Department of Bioengineering, School of Engineering, University of California, Los Angeles, CA 90095, USA; Terasaki Institute for Biomedical Innovation (TIBI), Los Angeles, CA 90024, USA.
Department of Bioengineering, School of Engineering, University of California, Los Angeles, CA 90095, USA.
California Nanosystems Institute, University of California, Los Angeles, CA 90095, USA; Department of Bioengineering, School of Engineering, University of California, Los Angeles, CA 90095, USA; Department of Mechanical and Aerospace Engineering, University of California, Los Angeles, CA 90095, USA.
Passarow Mass Spectrometry Laboratory, Semel Institute for Neuroscience and Behaviour, David Geffen School of Medicine, Los Angeles, CA 90095, USA.
California Nanosystems Institute, University of California, Los Angeles, CA 90095, USA.
California Nanosystems Institute, University of California, Los Angeles, CA 90095, USA; Department of Bioengineering, School of Engineering, University of California, Los Angeles, CA 90095, USA; Terasaki Institute for Biomedical Innovation (TIBI), Los Angeles, CA 90024, USA; Department of Chemical Engineering, School of Engineering, University of California, Los Angeles, CA 90095, USA; Department of Radiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Department of Bioengineering, School of Engineering, University of California, Los Angeles, CA 90095, USA; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095, USA.
University of South Florida College of Medicine, Tampa, FL 33612, USA.
Department of Integrative Biology and Physiology, University of California, CA 90095, USA; Department of Bioengineering, School of Engineering, University of California, Los Angeles, CA 90095, USA.
Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA; Department of Integrative Biology and Physiology, University of California, CA 90095, USA.
Department of Biological Chemistry and Center for Epigenetics and Metabolism, University of California, Irvine, CA 92697, USA.
Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; Department of Genetics, David Geffen School of Medicine, Los Angeles, CA 90095, USA.

Scar tissue size following myocardial infarction is an independent predictor of cardiovascular outcomes, yet little is known about factors regulating scar size. We demonstrate that collagen V, a minor constituent of heart scars, regulates the size of heart scars after ischemic injury. Depletion of collagen V led to a paradoxical increase in post-infarction scar size with worsening of heart function. A systems genetics approach across 100 in-bred strains of mice demonstrated that collagen V is a critical driver of postinjury heart function. We show that collagen V deficiency alters the mechanical properties of scar tissue, and altered reciprocal feedback between matrix and cells induces expression of mechanosensitive integrins that drive fibroblast activation and increase scar size. Cilengitide, an inhibitor of specific integrins, rescues the phenotype of increased post-injury scarring in collagen-V-deficient mice. These observations demonstrate that collagen V regulates scar size in an integrin-dependent manner.

中文翻译：

疤痕组织中的 V 型胶原蛋白可调节心脏损伤后疤痕的大小。

心肌梗塞后的疤痕组织大小是心血管结局的独立预测因素，但人们对调节疤痕大小的因素知之甚少。我们证明，V 型胶原蛋白是心脏疤痕的次要成分，可调节缺血性损伤后心脏疤痕的大小。 V 型胶原蛋白的消耗导致梗塞后疤痕尺寸反常增大，同时心脏功能恶化。对 100 只近交系小鼠进行的系统遗传学方法表明，V 型胶原蛋白是损伤后心脏功能的关键驱动因素。我们发现，V 型胶原蛋白缺乏会改变疤痕组织的机械特性，并且基质和细胞之间的相互反馈改变会诱导机械敏感性整合素的表达，从而驱动成纤维细胞活化并增加疤痕尺寸。西仑吉肽是一种特定整合素抑制剂，可挽救 V 型胶原蛋白缺陷小鼠损伤后疤痕增多的表型。这些观察结果表明，V 型胶原蛋白以整合素依赖性方式调节疤痕大小。

更新日期：2020-08-06

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11