New Insights into Hippo/YAP Signaling in Fibrotic Diseases

Cells. 2022 Jun 29;11(13):2065. doi: 10.3390/cells11132065.

Abstract

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.

Keywords: Hippo signaling; TAZ; YAP; adverse remodeling; fibroblast; myofibroblast; tissue fibrosis.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fibrosis
  • Hippo Signaling Pathway
  • Humans
  • Myofibroblasts / metabolism
  • Protein Serine-Threonine Kinases*
  • Signal Transduction* / physiology

Substances

  • Protein Serine-Threonine Kinases

Grants and funding

This work was supported by funds from Duke-NUS Medical School Singapore and the Goh foundation and an NMRC grant (MOH-000025) to M.K.S.