Cellular mechanotransduction in health and diseases: from molecular mechanism to therapeutic targets

Signal Transduction and Targeted Therapy · 9 authors, 2 centres

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This narrative review summarizes the molecular mechanisms of cellular mechanotransduction, detailing key effectors and pathways that convert mechanical stimuli into biochemical signals.

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This narrative review synthesizes current knowledge on cellular mechanotransduction, the process by which cells convert mechanical stimuli into biochemical signals. It describes typical mechanical cues such as hydrostatic pressure, fluid shear stress, and extracellular matrix stiffness, and lists key molecular effectors like Piezo channels, integrins, YAP/TAZ, and TRPV4, along with signaling pathways including TGFβ/Smad and RhoA/ROCK.

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narrative_review

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biomedical research

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ORIGINAL PAPER

PMC10387486

Cellular mechanotransduction in health and diseases: from molecular mechanism to therapeutic targets

Signal Transduction and Targeted Therapy

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ABSTRACT

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.

CITATION EXPORT

Xingpeng Di, Xiaoshuai Gao, Liao Peng et al.. Cellular mechanotransduction in health and diseases: from molecular mechanism to therapeutic targets. Signal Transduction and Targeted Therapy. (2023). https://doi.org/10.1038/s41392-023-01501-9

AUTHORS

9 · 2 CENTRES

Xingpeng Di, Xiaoshuai Gao, Liao Peng, Jianzhong Ai, Xi Jin, Shiqian Qi, Hong Li, Kunjie Wang, Deyi Luo

1grid.13291.380000 0001 0807 1581Department of Urology and Institute of Urology, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, P.R. China
2grid.13291.380000 0001 0807 1581State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, P.R. China