Piezo mechanosensitive channels: A biological hub for intestinal barrier homeostasis and an emerging target for disease intervention

Table 3 Pathogenic mechanisms of piezo in irritable bowel syndrome

Pathogenic mechanism	Related pathways	Specific effect
Intestinal barrier disruption	Mechanical stimulation induces upregulation of Piezo1, activates ROCK1/2, and inhibits claudin1 expression[33]	The abnormal increase in intestinal epithelial permeability and impaired barrier function exacerbates the intestinal inflammatory response
	Activation of goblet cell Piezo1, inhibition of SUV39h1, downregulation of H3K9me3, and upregulation of mucin2 transcription[30]	Alteration of intestinal flora; abnormal mucus secretion and impaired barrier function
Visceral hypersensitivity	Mechanical stimulation activates EC cells Piezo2, releasing 5-HT, which activates 5-HT3 receptors in sensory nerves to transmit nociceptive signals[53,57,78-80]	Acute and persistent pain
	Pathological stimulation of DRG neurons leads to Piezo2 activation, Ca2+ influx, enhanced CREB/Akt signaling, and promotion of CGRP release[15,59,81]	Spinal cord central sensitization causes mild mechanical stimuli to be perceived as pain, which further progresses into chronic persistent visceral pain
	Piezo2 is expressed in the TRPV1 family of nociceptors in the colon, responding to mechanical distension[15,82-85]	Pathomechanical hyperalgesia
Neuroendocrine dysfunction	Piezo2 detects mechanical stimuli, which stimulate EC cells to release increased 5-HT, leading to the corresponding symptoms of IBS[86-89]	Intermittent abdominal pain and abdominal distension; alternating diarrhea and constipation
	Piezo2 detects mechanical stimuli, which stimulate EC cells to release increased 5-HT, leading to serotonin signaling dysfunction in the gut-brain axis[78,86]	Abnormal intestinal-brain interaction; extraintestinal symptoms such as psychiatric disorders

ROCK1/2: Rho-associated coiled-coil containing protein kinase 1/2; SUV39h1: Suppressor of variegation 3-9 homolog 1; ECs: Enterochromaffin cells; 5-HT: 5-hydroxytryptamine; DRG: Dorsal root ganglion; CREB: CAMP-response element binding protein; Akt: Protein kinase B; CGRP: Calcitonin gene-related peptide; TRPV1: Transient receptor potential vanilloid 1; IBS: Irritable bowel syndrome.