RNA Sensing by Gut Piezo1 Is Essential for Systemic Serotonin Synthesis

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On July 7, 2020, professor Kenta Maruyama from Osaka University WPI Immunology Frontier Research Center published a paper on Cell. The paper titled RNA Sensing by Gut Piezo1 Is Essential for Systemic Serotonin Synthesis.


The ELISA kit (CTX1, CEA665Mu) of Cloud-Clone brand was chosed to determine the concentation of PVR in this article, we are so proud for supporting the reaserchers.

Gastrointestinal enterochromaffin cells regulate bone and gut homeostasis via serotonin (5-hydroxytryptamine [5-HT]) production. A recent report suggested that gut microbes regulate 5-HT levels; however, the precise underlying molecular mechanisms are unexplored. Here, we reveal that the cation channel Piezo1 in the gut acts as a sensor of single-stranded RNA (ssRNA) governing 5-HT production. Intestinal epithelium-specific deletion of mouse Piezo1 profoundly disturbed gut peristalsis, impeded experimental colitis, and suppressed serum 5-HT levels. Because of systemic 5-HT deficiency, conditional knockout of Piezo1 increased bone formation. Notably, fecal ssRNA was identified as a natural Piezo1 ligand, and ssRNA-stimulated 5-HT synthesis from the gut was evoked in a MyD88/TRIF-independent manner. Colonic infusion of RNase A suppressed gut motility and increased bone mass. These findings suggest gut ssRNA as a master determinant of systemic 5-HT levels, indicating the ssRNA-Piezo1 axis as a potential prophylactic target for treatment of bone and gut disorders.