The mechanobiology of fibroblast activation in disease.

IF 6.6 3区 医学 Q1 ENGINEERING, BIOMEDICAL
APL Bioengineering Pub Date : 2025-06-18 eCollection Date: 2025-06-01 DOI:10.1063/5.0272393
Yeji Chang, Jia Wen Nicole Lee, Andrew W Holle
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Abstract

Fibroblasts play crucial roles in wound healing, cancer, and fibrosis. Many aspects of these roles are driven by the process known as fibroblast activation. The generally accepted definition of fibroblast activation is the transition from a quiescent state to a state in which fibroblasts participate in a number of active processes, including extracellular matrix (ECM) production and remodeling, elevated contractility, and enhanced migratory capacity, although there is no universal consensus on what exactly constitutes "activation." Interestingly, the time scale of activation is not consistent across tissues and disease states; some fibroblasts quickly return to quiescence after activation (e.g., in wound healing), others undergo apoptosis, while a subset become persistently activated. This activation, both acute and persistent, is inherently a mechanical process, given the increase in ECM production and remodeling and the enhanced traction force generation. Thus, there exists a dynamic reciprocity, or cell-ECM feedback, in which activated fibroblasts produce a mechanical microenvironment that in turn supports persistent activation. This has a wide variety of implications for disease, most notably fibrosis and cancer, as the fibroblasts that become persistently activated in connection with these conditions can contribute to disease state progression. Like other mechanosensitive processes, this mechanically induced persistent fibroblast activation is driven by a number of mechanotransduction signaling pathways. Thus, an opportunity exists in which the mechanosensitive underpinning of fibroblast activation can be leveraged to improve clinical outcomes. Here, we highlight these opportunities and make a call to the field to consider the mechanosensitive pathways governing fibroblast activation as an important frontier in mechanomedicine.

成纤维细胞在疾病中活化的机械生物学。
成纤维细胞在伤口愈合、癌症和纤维化中起关键作用。这些作用的许多方面是由称为成纤维细胞激活的过程驱动的。普遍接受的成纤维细胞激活的定义是从静止状态过渡到成纤维细胞参与一些活跃过程的状态,包括细胞外基质(ECM)的产生和重塑、收缩性的提高和迁移能力的增强,尽管对于什么是“激活”还没有普遍的共识。有趣的是,激活的时间尺度在不同组织和疾病状态下并不一致;一些成纤维细胞在激活后迅速恢复平静(例如,在伤口愈合中),其他的发生细胞凋亡,而一个子集持续激活。这种激活,无论是急性的还是持续的,本质上是一个机械过程,因为ECM产生和重塑的增加以及牵引力产生的增强。因此,存在一种动态相互作用,或细胞- ecm反馈,其中活化的成纤维细胞产生一个机械微环境,反过来支持持续激活。这对疾病有各种各样的影响,尤其是纤维化和癌症,因为与这些疾病相关的成纤维细胞持续激活可以促进疾病状态的进展。像其他机械敏感过程一样,这种机械诱导的持续成纤维细胞激活是由许多机械转导信号通路驱动的。因此,有机会利用成纤维细胞活化的机械敏感性基础来改善临床结果。在这里,我们强调了这些机会,并呼吁该领域将控制成纤维细胞激活的机械敏感途径视为机械医学的重要前沿。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
APL Bioengineering
APL Bioengineering ENGINEERING, BIOMEDICAL-
CiteScore
9.30
自引率
6.70%
发文量
39
审稿时长
19 weeks
期刊介绍: APL Bioengineering is devoted to research at the intersection of biology, physics, and engineering. The journal publishes high-impact manuscripts specific to the understanding and advancement of physics and engineering of biological systems. APL Bioengineering is the new home for the bioengineering and biomedical research communities. APL Bioengineering publishes original research articles, reviews, and perspectives. Topical coverage includes: -Biofabrication and Bioprinting -Biomedical Materials, Sensors, and Imaging -Engineered Living Systems -Cell and Tissue Engineering -Regenerative Medicine -Molecular, Cell, and Tissue Biomechanics -Systems Biology and Computational Biology
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