Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, 8 College Road, Office 08-15, Singapore 169857, Singapore.
National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore 169609, Singapore.
Cells. 2022 Jun 29;11(13):2065. doi: 10.3390/cells11132065.
Fibrosis results from defective wound healing processes often seen after chronic injury and/or inflammation in a range of organs. Progressive fibrotic events may lead to permanent organ damage/failure. The hallmark of fibrosis is the excessive accumulation of extracellular matrix (ECM), mostly produced by pathological myofibroblasts and myofibroblast-like cells. The Hippo signaling pathway is an evolutionarily conserved kinase cascade, which has been described well for its crucial role in cell proliferation, apoptosis, cell fate decisions, and stem cell self-renewal during development, homeostasis, and tissue regeneration. Recent investigations in clinical and pre-clinical models has shown that the Hippo signaling pathway is linked to the pathophysiology of fibrotic diseases in many organs including the lung, heart, liver, kidney, and skin. In this review, we have summarized recent evidences related to the contribution of the Hippo signaling pathway in the development of organ fibrosis. A better understanding of this pathway will guide us to dissect the pathophysiology of fibrotic disorders and develop effective tissue repair therapies.
纤维化是由于慢性损伤和/或炎症后一系列器官的愈合过程出现缺陷所致。进行性纤维化事件可能导致永久性器官损伤/衰竭。纤维化的标志是细胞外基质(ECM)的过度积累,主要由病理性肌成纤维细胞和肌成纤维细胞样细胞产生。Hippo 信号通路是一条进化上保守的激酶级联反应,它在细胞增殖、凋亡、细胞命运决定以及发育、稳态和组织再生过程中的干细胞自我更新中发挥着至关重要的作用,这一点已经得到了很好的描述。临床前和临床模型的最近研究表明,Hippo 信号通路与包括肺、心、肝、肾和皮肤在内的许多器官的纤维化疾病的病理生理学有关。在这篇综述中,我们总结了与 Hippo 信号通路在器官纤维化发展中的作用相关的最新证据。更好地了解这一途径将有助于我们剖析纤维化疾病的病理生理学,并开发有效的组织修复疗法。