摘要：

Mechanosensing is involved in almost all physiological processes and is implicated in ageing and neurodegenerative diseases. The identification of mechanotransduction ion channels over the past decade has made significant impact in the emerging field of mechanobiology. Although we have gained insights into the stretch-sensitive ion channels (e.g., Piezo) and their contributions to physiological processes such as gentle touch sensation, many fundamental questions in mechanobiology remain unsolved. For example, mechanisms of mechanical nociception are poorly understood, and hence mechanical pain is considered the last frontier of sensory neurobiology. What are the ion channels that regulate mechanical nociception and what are the forces involved in nociceptor activation? We address these problems by unraveling a role of shear stress in activation of nociceptors and further identify TrpA1 as a shear stress sensor underlying this process. In addition to sensing external stimuli, shear stress is a natural stimulus for many tissues including the gastrointestinal tract. We found that enteroendocrine cells specifically respond to shear stress through TrpA1. Strikingly, shear stress mechanosensing by enteroendocrine cells could profoundly regulate intestine stem cell behavior and gut tissue homeostasis. Because gut homoeostasis is essential for the gut to interact with other tissues including the nervous system, this finding would set up the foundation for future investigation of how gut mechanosensing could regulate the gut-brain axis.

Reference

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