小柯机器人

日本大阪大学Kenta Maruyama研究组发现，肠道Piezo1感知RNA对系统性5 -羟色胺（5-HT）的合成至关重要。该研究成果于2020年7月7日在线发表在《细胞》上。

研究人员发现肠道中的阳离子通道Piezo1作为单链RNA（ssRNA）感受器来调控5-HT的产生。小鼠肠上皮细胞Piezo1特异性缺失极大地干扰了肠蠕动、阻碍了实验性结肠炎、并抑制了血清5-HT的水平。由于全身5-HT缺乏，Piezo1的条件性敲除会增加骨形成。

值得注意的是，研究表明粪便中的ssRNA是Piezo1的天然配体，并且以MyD88 / TRIF不依赖的方式引发肠道中ssRNA诱导的5-HT合成。结肠灌注RNase A可抑制肠蠕动并增加骨量。这些发现表明肠道ssRNA是全身5-HT水平的主要决定因素，并揭示了ssRNA-Peizo1轴可作为骨和肠道疾病治疗的潜在靶标。

据介绍，胃肠道肠嗜铬细胞通过产生5-羟色胺来调控骨骼和肠道稳态。最近的研究表明，肠道微生物可调节5-HT水平。然而，确切的分子机制尚待探究。

附：英文原文

Title: RNA Sensing by Gut Piezo1 Is Essential for Systemic Serotonin Synthesis

Author: Erika Sugisawa, Yasunori Takayama, Naoki Takemura, Takeshi Kondo, Shigetsugu Hatakeyama, Yutaro Kumagai, Masataka Sunagawa, Makoto Tominaga, Kenta Maruyama

Issue&Volume: 2020-07-07

Abstract: 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-Peizo1 axis as a potential prophylactic target for treatment of bone and gut disorders.

DOI: 10.1016/j.cell.2020.06.022

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30754-6