A novel role of Hippo-Yap/TAZ signaling pathway in lymphatic vascular development

Abstract

The lymphatic vasculature plays important role in regulating fluid homeostasis, intestinal lipid absorption, and immune surveillance in humans. Malfunction of lymphatic vasculature leads to several human diseases. Understanding the fundamental mechanism in lymphatic vascular development not only expand our knowledge, but also provide a new therapeutic insight. Recently, Hippo-YAP/TAZ signaling pathway, a key mechanism of organ size and tissue homeostasis, has emerged as a critical player that regulate lymphatic specification, sprouting, and maturation. In this review, we discuss the mechanistic regulation and pathophysiological significant of Hippo pathway in lymphatic vascular development. [

Synthetic hyaluronic acid coating preserves the phenotypes of lymphatic endothelial cells

“…63 Recent studies described that YAP/TAZ work as stress-mediated mechanotransducers in LECs like that of BECs but different in that YAP/TAZ regulate Prox1 transcriptional activity in LECs. 79,80 Strikingly, lymphatic YAP/TAZ negatively regulate Prox1 transcription, and they modulate Prox1 activity and lymphatic plasticity. 63 Consistent to previous findings, our data also suggest that culturing LECs on HA-DP coated plates causes cytoplasmic degradation of YAP/TAZ, which subsequently enhances transcription of lymphatic master regulator Prox1, including its targets LYVE-1, PDPN, and VEGFR3.…”

The emerging roles of long noncoding RNAs in lymphatic vascular development and disease

“…For instance, Hippo signaling negatively regulates PROX1 expression during LEC specification and sprouting [ 191 ]. In line with this, it has been proposed that the Hippo signaling effectors YAP/TAZ play a role in the PROX1/VEGFR-3 feedback loop during LEC specification and migration and lymphatic valve maturation [ 192 ].…”

The role of lacteal integrity and junction transformation in obesity: A promising therapeutic target?

“…Only button-like junctions were observed at ten weeks of age in mice while developing initial lymphatic vessels first had zipper-like junctions in the embryos of mice ( 41 ). Several studies uncovered that the underlying mechanism by which zipper-like junctions converted into button-like junctions postnatally might be associated with VE-cadherin regulation by angiopoietin2 (ANG2) and Hippo signaling ( 40 , 42 , 43 ).…”

“…In addition to Angiopoietin-TIE signaling, Hippo signaling seems to participate in junction transformation. In recent studies, Hippo signaling has been demonstrated to regulate the proliferation and homeostasis of LECs ( 42 , 46 , 47 ). YAP/TAZ is the terminal transcriptional regulator of Hippo signaling, binding TEA domain transcription factors (TEADs) to mediate relative target genes in lymphangiogenesis ( 42 ).…”

“…In recent studies, Hippo signaling has been demonstrated to regulate the proliferation and homeostasis of LECs ( 42 , 46 , 47 ). YAP/TAZ is the terminal transcriptional regulator of Hippo signaling, binding TEA domain transcription factors (TEADs) to mediate relative target genes in lymphangiogenesis ( 42 ). An exciting study revealed that PDGFRβ+ intestinal stromal cells (IntSCs) maintained lacteal integrity and function by YAP/TAZ-dependent secretion of VEGF-C ( 43 ).…”