Language

English

Publication Date

8-18-2025

Journal

Genes

DOI

10.3390/genes16080968

PMID

40870015

PMCID

PMC12385653

PubMedCentral® Posted Date

8-18-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Mechanotransduction, also referred to as mechano-signal transduction, is a biophysical process wherein cells perceive and respond to mechanical stimuli by converting them into biochemical signals that initiate specific cellular responses. This mechanism is fundamental to the development and growth, and proper functioning of mechanically active tissues, such as the diaphragm-a respiratory muscle vital for breathing in mammals. In vivo, the diaphragm is subjected to transdiaphragmatic pressure, and therefore, its muscle fibers are subjected to mechanical forces not only in the direction of the muscle fibers but also in the direction transverse to the fibers. Previous research conducted in our laboratory uncovered that stretching the diaphragm in either the longitudinal or transverse direction activates distinct mechanotransduction pathways. This indicates that signaling pathways in the diaphragm muscle are regulated in an anisotropic manner. In this review paper, we discussed the underlying mechanisms that regulate the anisotropic signaling pathways in the diaphragmatic muscle, emphasizing the mechanical role of cytoskeletal proteins in this context. Furthermore, we explored the regulatory mechanisms governing mechanosensitive gene transcription, including microRNAs (mechanomiRs), within the diaphragm muscle. Finally, we examined potential links between anisotropic signaling in the diaphragm muscle and various skeletal muscle disorders.

Keywords

Diaphragm, Animals, Mechanotransduction, Cellular, Humans, Cytoskeleton, Signal Transduction, MicroRNAs, anisotropic gene regulation, mechanical stretch, mechanotransduction, skeletal muscle, cytoskeletal proteins, mechanomiRs

Published Open-Access

yes

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