Response to Mechanical Cues by Interplay of YAP/TAZ Transcription Factors and Key Mechanical Checkpoints of the Cell:A Comprehensive Review

Abstract

Many factors including growth factors (GF), scaffold materials, and chemical and physical cues determine the cell behaviors. For many years, growth factors have been considered as the pivotal cell behavior regulators, whereas recent studies emphasize also the key role of physical factors such as mechanical forces, cell shape, surface topographies, and extracellular matrix (ECM) in regulating the cell proliferation, apoptosis, differentiation, etc. through mechanotransduction pathways. In this process, the cell morphology and mechanical properties of the cell's micro/ nano-environments and ECM can be conveyed to the nucleus by regulating transcriptional factors such as Yes-associated protein and transcriptional coactivator with PDZ-binding motif (TAZ). Generally, YAP/TAZ activity is considered as the key factor for the growth of whole organs, however, recent studies have also repeatedly addressed the role of YAP/TAZ in mechanotransduction. In this review, the biological functions of the YAP/TAZ pathway and its contribution to the mechanotransduction and cell behavior regulation in response to the mechanical cues have been summarized. Also, the role of key mechanical checkpoints in the cell including focal adhesions, cytoskeletal tension, Rho small GTPases, and nuclear membrane protein elements involved in the transfer of environmental mechanical cues from the cell surface to the nucleus and their effect in regulating the YAP/TAZ activity are discussed.

Endothelial upregulation of mechanosensitive channel Piezo1 in pulmonary hypertension

“…Endothelial YAP/TAZ signaling is an important pathway for angiogenesis and tumor vascularization (92), pulmonary fibrosis (93,94), and production of endothelin-1 (95), an endothelium-derived constricting factor (EDCF) that causes pulmonary vasoconstriction and vascular remodeling (96)(97)(98)(99) and RV hypertrophy (100). One of the downstream signaling pathways of Piezo1/2-mediated mechanotransduction is the YAP signaling pathway (101)(102)(103)(104)(105). The HIPPO effector Yap1 and the Notch signaling are essential for Zebrafish outflow tract valve morphogenesis in response to mechanical forces; Piezo controls Klf2 and Notch activity in the endothelium and Yap1 localization in smooth muscle progenitor cells to coordinate outflow tract valve formation (106).…”

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“…This work was done for providing insights into a form of vitamin B3; nicotinic acid (NA), in oil and water environments. It was earlier mentioned that explorations of biological related systems are very important due to several reasons from appearing the new diseases or the wildness of already known ones [80][81][82][83]. Not only the direct treatments of patients, but also several other issues are needed for dealing with the biological systems for keeping the human health systems and levels [84][85][86][87].…”

An inspired microenvironment of cell replicas to induce stem cells into keratocyte-like dendritic cells for corneal regeneration

“…These ECM properties can influence cellular behavior such as proliferation and differentiation via mechanotransduction pathways 15 . During physical differentiation, cytoskeletal reorganization is activated by inducers like micro-/nano topography surface features and cells geometry which are related to activation of mechanical cues, formation of mature focal adhesion complex, protein kinases, actin filament assembly, nucleus deformation, and finally gene regulation of stem cells 33 , 35 . Meanwhile, the exact reason of transmitting extracellular topography to intracellular biological processes is still indistinct.…”