The Roles of YAP/TAZ and the Hippo Pathway in Healthy and Diseased Skin

Abstract

Skin is the largest organ of the human body. Its architecture and physiological functions depend on diverse populations of epidermal cells and dermal fibroblasts. Reciprocal communication between the epidermis and dermis plays a key role in skin development, homeostasis and repair. While several stem cell populations have been identified in the epidermis with distinct locations and functions, there is additional heterogeneity within the mesenchymal cells of the dermis. Here, we discuss the current knowledge of how the Hippo pathway and its downstream effectors Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) contribute to the maintenance, activation and coordination of the epidermal and dermal cell populations during development, homeostasis, wound healing and cancer.

SLIT3 deficiency attenuates pressure overload–induced cardiac fibrosis and remodeling

“…The findings of this study are especially relevant to children with congenital heart disease or pulmonary hypertension who are chronically exposed to either left or right ventricular pressure overload and whose outcomes are dependent upon the maintenance of ventricular function. Importantly, children with pressure overload of the right ventricle have no effective medical treatment beyond heart transplantation (1, 6), and thus targeting SLIT3 or fibroblast-specific YAP1 activation (59,98,99), rather than cardiomyocyte-specific YAP1 activation (100), may a promising strategy to inhibit adverse remodeling and preserve ventricular function by reducing fibrosis (101). Furthermore, MI is rare in children, and hence myocardial rupture after infarction as a potential side effect of SLIT3 inhibition would be unusual in children with ventricular pressure overload.…”

Role of the Hippo Pathway in Fibrosis and Cancer

“…YAP also plays an important role in maintaining normal skin homeostasis in response to extracellular cues by promoting cell proliferation in epidermal stem and progenitor cells, and tissue expansion [80,81] Genetic analysis showed that YAP is highly expressed and shows nuclear localization in epidermal progenitor and stem cells, revealing a requirement for TEAD to mediate YAP’s functions in controlling their self-renewal and maintaining their undifferentiated state [82]. Moreover, enhanced nuclear YAP/TAZ levels have been detected in the dermis during the skin wound-healing process.…”

Long non-coding RNAs in cutaneous biology and keratinocyte carcinomas

“…Hippo pathway is a well-conserved signaling pathway, which is important in skin development, cutaneous homeostasis and tissue regeneration, and aberrant Hippo signaling has been noted in non-melanoma skin cancers [125]. Recently, upregulation of a previously unknown lncRNA, LINC01048, was reported in cSCC associated with lower overall survival of cSCC patients [126].…”