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

Figure 1 Piezo regulates intestinal mucosal and epithelial barrier through multiple signaling pathways. A: In the mucosal barrier, Piezo1 promotes Mucin2 secretion via the extracellular signal-regulated kinase/Ca²⁺ pathway and inhibits the suppressor of variegation 3-9 homolog 1-histone H3 lysine 9 trimethylation pathway; B: In the epithelial barrier, Piezo1 suppresses Claudin-1 expression through Rho-associated coiled-coil containing protein kinase 1/2, mediates Ca²⁺ influx-induced mitochondrial dysfunction, and inhibits the adenosine monophosphate-activated protein kinase/mechanistic target of rapamycin pathway in its absence. Besides, it enhances glucagon-like peptide-1 synthesis to maintain blood glucose levels and reduces dietary lipid absorption efficiency via calmodulin-dependent protein kinase II. ERK: Extracellular signal-regulated kinase; Me: Methyl group; SUV39h1-H3K9me3: Suppressor of variegation 3-9 homolog 1-histone H3 lysine 9 trimethylation; ROCK1/2: Rho-associated coiled-coil containing protein kinase 1/2; AMPK: Adenosine monophosphate-activated protein kinase; mTOR: Mechanistic target of rapamycin; GPX4: Glutathione peroxidase 4; GLP-1: Glucagon-like peptide-1; DGAT2: Diacylglycerol O-acyltransferase 2; CaMKII: Calmodulin-dependent protein kinase II; AMPKα: Adenosine monophosphate-activated protein kinase alpha subunit; CD36: Cluster of differentiation 36.