Relationship between Keloid Formation and YAP/TAZ Signaling

Abstract

Summary:YAP (yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif) are part of a classical pathway that controls contact inhibition in the Hippo pathway. YAP and TAZ were recently reported to act as nuclear relays of mechanical signals that communicate extracellular matrix rigidity and cell shape. However, the role of YAP/TAZ signaling in keloid formation is unclear. Here, we used immunohistochemistry to investigate YAP/TAZ expression in keloid and nonaffected lesions. YAP/TAZ expression in keloid fibroblasts had a greater tendency to localize to the nucleus relative to that seen in fibroblasts from unaffected tissues. Meanwhile, keratinocytes or endothelial cells from either keloid or unaffected tissues showed no significant differences in YAP/TAZ expression patterns. These results suggest that YAP/TAZ nuclear localization in keloid fibroblasts might activate Hippo signaling and may play an important role in gene expression that affects keloid formation and stiffness.

Targeted inhibition of YAP/TAZ alters the biological behaviours of keloid fibroblasts

“…Moreover, YAP/TAZ have been found to be associated with lung fibrosis and systemic sclerosis fibrosis 23,24 . In a recent study, keloid dermal fibroblasts were found to express increased nuclear YAP/TAZ compared to fibroblasts in the adjacent healthy tissue 12 . Thus, we performed this study to explore the links between YAP/TAZ and the biological behaviour of fibroblasts.…”

“…To date, Hippo signalling has been implicated in the pathogenesis of many human diseases including cancer and fibrosis 4,9–11 . Increased nuclear YAP/TAZ staining has also been found in keloid fibroblasts compared to the adjacent normal skin fibroblasts 12 . Our current study thus aims to evaluate the effect of YAP/TAZ inhibition on proliferation, migration, apoptosis, and collagen production of keloid fibroblasts.…”

Determination the Effect of YAP/TAZ Signaling Pathway on Mechanical Stress Induced Hypertrophic Scar Formation by GEO2R

“…10 lenip, yara iyileşmesi tamamlandıktan sonra sitoplazmada gözlenmektedir. 25 HTS oluşumunda, YAP/TAZ sinyal yolağının rolüne ilişkin çalışmalara rastlanmamaktadır. Keloids skarlarda (yara bölgesinin sınırlarının dışına taşarak daha geniş bir yüzeye yayılması ile HTS'den ayrılmaktadır.)…”

Glutaminase inhibitors rejuvenate human skin via clearance of senescent cells: a study using a mouse/human chimeric model

“…GAPDH (Hs02786624_g1) was used as an endogenous control. For in vitro analysis, GAPDH expression in the proliferating cell population was used AGING as the baseline; for in vivo analysis, cDNA purified from mRNA previously collected from the normal human skin of a 10-year-old male was used as the relative baseline [39].…”