| First Author | Sugisawa E | Year | 2020 |
| Journal | Cell | Volume | 182 |
| Issue | 3 | Pages | 609-624.e21 |
| PubMed ID | 32640190 | Mgi Jnum | J:305290 |
| Mgi Id | MGI:6705892 | Doi | 10.1016/j.cell.2020.06.022 |
| Citation | Sugisawa E, et al. (2020) RNA Sensing by Gut Piezo1 Is Essential for Systemic Serotonin Synthesis. Cell 182(3):609-624.e21 |
| abstractText | 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. |
