摘要
Cellular mechanotransduction,a critical regulator of numerous biological processes,is the conversion from mechanical signals to biochemical signals regarding cell activities and metabolism.Typical mechanical cues in organisms include hydrostatic pressure,fluid shear stress,tensile force,extracellular matrix stiffness or tissue elasticity,and extracellular fluid viscosity.Mechanotransduction has been expected to trigger multiple biological processes,such as embryonic development,tissue repair and regeneration.However,prolonged excessive mechanical stimulation can result in pathological processes,such as multi-organ fibrosis,tumorigenesis,and cancer immunotherapy resistance.Although the associations between mechanical cues and normal tissue homeostasis or diseases have been identified,the regulatory mechanisms among different mechanical cues are not yet comprehensively illustrated,and no effective therapies are currently available targeting mechanical cue-related signaling.This review systematically summarizes the characteristics and regulatory mechanisms of typical mechanical cues in normal conditions and diseases with the updated evidence.The key effectors responding to mechanical stimulations are listed,such as Piezo channels,integrins,Yes-associated protein(YAP)/transcriptional coactivator with PDZ-binding motif(TAZ),and transient receptor potential vanilloid 4(TRPV4).We also reviewed the key signaling pathways,therapeutic targets and cutting-edge clinical applications of diseases related to mechanical cues.
基金
This work was supported by the National Science Fund of China(Grant Number:82270720)
National Clinical Research Center for Geriatrics,West China Hospital,Sichuan University(Grant Number:Y2021LC005)
1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(Grant Number:ZYGD18011)
The National Science Fund of China(Grant Number:81873601).Many thanks to ClinicalTrials.gov(https://clinicaltrials.gov/ct2/home),which is maintained by the National Library of Medicine(NLM)at the National Institutes of Health(NIH),for the support of clinical trials collection.We appreciate the support from Biorender(https://www.biorender.com)for helping us create some of the figures.We thank Xintong Bao for her kind and excellent help in this study。
