Disrupting biological sensors of force promotes tissue regeneration in large organisms.
Disrupting biological sensors of force promotes tissue regeneration in large organisms.
复制标题
DOI：
10.1038/s41467-021-25410-z
复制
发表时间：
2021-09-06
影响因子：
16.6
通讯作者：
Gurtner GC
中科院分区：
文献类型：
--
作者：
Chen K;Kwon SH;Henn D;Kuehlmann BA;Tevlin R;Bonham CA;Griffin M;Trotsyuk AA;Borrelli MR;Noishiki C;Padmanabhan J;Barrera JA;Maan ZN;Dohi T;Mays CJ;Greco AH;Sivaraj D;Lin JQ;Fehlmann T;Mermin-Bunnell AM;Mittal S;Hu MS;Zamaleeva AI;Keller A;Rajadas J;Longaker MT;Januszyk M;Gurtner GC
组织修复和愈合仍然是出生后生命中最复杂的过程之一。人类和其他大型生物体通过形成功能减弱的纤维化瘢痕组织来愈合，而较小的生物体则通过无瘢痕组织再生和功能恢复来应对。完善的缩放原则表明，生物体大小与运动过程中的峰值组织力呈指数相关，进化反应通过加强器官水平的机械性能进行补偿。这些适应性变化如何影响组织损伤以前尚未在大型动物和人类中进行过研究。在这里，我们表明，通过在大型动物中的粘着斑激酶通路阻断机械转导信号显着加速伤口愈合，并增强皮肤的再生与二级结构，如毛囊。在人类细胞中，我们证明机械力使成纤维细胞在ERK-YAP激活的驱动下转向促纤维化表型，导致肌成纤维细胞分化和过量胶原蛋白产生。机械信号传导的破坏特异性地消除这些反应，而是促进以AKT-EGR 1为特征的再生成纤维细胞簇。人类和其他大型哺乳动物通过形成功能减弱的纤维化瘢痕组织来愈合伤口。在这里，作者表明，通过在大型动物中破坏粘着斑激酶途径的机械转导，加速愈合，防止纤维化，并增强皮肤再生。
Tissue repair and healing remain among the most complicated processes that occur during postnatal life. Humans and other large organisms heal by forming fibrotic scar tissue with diminished function, while smaller organisms respond with scarless tissue regeneration and functional restoration. Well-established scaling principles reveal that organism size exponentially correlates with peak tissue forces during movement, and evolutionary responses have compensated by strengthening organ-level mechanical properties. How these adaptations may affect tissue injury has not been previously examined in large animals and humans. Here, we show that blocking mechanotransduction signaling through the focal adhesion kinase pathway in large animals significantly accelerates wound healing and enhances regeneration of skin with secondary structures such as hair follicles. In human cells, we demonstrate that mechanical forces shift fibroblasts toward pro-fibrotic phenotypes driven by ERK-YAP activation, leading to myofibroblast differentiation and excessive collagen production. Disruption of mechanical signaling specifically abrogates these responses and instead promotes regenerative fibroblast clusters characterized by AKT-EGR1. Humans and other large mammals heal wounds by forming fibrotic scar tissue with diminished function. Here, the authors show that disrupting mechanotransduction through the focal adhesion kinase pathway in large animals accelerates healing, prevents fibrosis, and enhances skin regeneration.
登录
查看更多内容
DOI：
10.1186/1755-1536-5-15
发表时间：
2012-09-03
期刊：
Fibrogenesis & tissue repair
影响因子：
--
作者：
Fan D;Takawale A;Lee J;Kassiri Z
通讯作者：
Kassiri Z
影响因子：
64.8
作者：
Cao, Junyue;Spielmann, Malte;Shendure, Jay
通讯作者：
Shendure, Jay
影响因子：
46.9
作者：
Becht, Etienne;McInnes, Leland;Newell, Evan W.
通讯作者：
Newell, Evan W.
影响因子：
56.9
作者：
BIEWENER, AA
通讯作者：
BIEWENER, AA
影响因子：
4.8
作者：
Aarabi, Shahram;Bhatt, Kirit A.;Gurtner, Geoffrey C.
通讯作者：
Gurtner, Geoffrey C.