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

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.

Cyclic stretch induced epigenetic activation of periodontal ligament cells

“…This intricate machinery encompasses several major components spanning the cell membrane, cytosolic compartments, and even intranuclear space [ 3 , 11 ]. Key contributors such as focal adhesions, cytoskeletal elements, and the nuclear envelope (lamins) collectively facilitate communication between the extracellular matrix niche and the genome to activate mechanoresponsive programs [ 6 , [12] , [13] , [14] , [15] , [16] ]. Forces transmitted across these pathways have been demonstrated to elicit epigenetic alterations capable of directing cell identity processes including survival, differentiation, and cell cycle regulation in diverse cell types ranging from stem cells to specialized chondrocytes, tenocytes, alveolar cells and even cancer lines [ [17] , [18] , [19] , [20] , [21] ].…”

Spatiotemporal multi-omics: exploring molecular landscapes in aging and regenerative medicine

“…Cell differentiation marks the transformation of cells from an undifferentiated state into specialized cell types, such as muscle or nerve cells [ 220 , 221 ]. Pattern formation of regenerating organs refers to the capacity of newly generated tissues or organs to develop in a specific sequence and arrangement during the regeneration process [ 226 , 227 ]. Governing the regeneration process is an array of influential factors, encompassing genes (i.e, MSX , p53 , HOX ) [ 228 – 233 ], environmental elements (i.e .…”

Effects of mechanical ventilation on the interstitial extracellular matrix in healthy lungs and lungs affected by acute respiratory distress syndrome: a narrative review

“…Integrins, transmembrane receptors that facilitate cell–ECM adhesion, act as intermediaries in mechanochemical communication [ 8 ]. In response to mechanical cues generated during mechanical ventilation, integrins transduce signals that regulate processes ranging from cell survival to inflammation [ 9 ]. The composition and spatial organization of the ECM influence integrin-mediated signaling, thereby contributing to the intricate orchestration of inflammatory responses and tissue repair [ 10 ].…”