腸道Piezo1感知RNA對系統性5 -羥色胺的合成至關重要
作者：
小柯機器人發布時間：2020/7/9 9:36:45
日本大阪大學Kenta Maruyama研究組發現，腸道Piezo1感知RNA對系統性5 -羥色胺（5-HT）的合成至關重要。該研究成果於2020年7月7日在線發表在《細胞》上。
研究人員發現腸道中的陽離子通道Piezo1作為單鏈RNA（ssRNA）感受器來調控5-HT的產生。小鼠腸上皮細胞Piezo1特異性缺失極大地幹擾了腸蠕動、阻礙了實驗性結腸炎、並抑制了血清5-HT的水平。由於全身5-HT缺乏，Piezo1的條件性敲除會增加骨形成。
值得注意的是，研究表明糞便中的ssRNA是Piezo1的天然配體，並且以MyD88 / TRIF不依賴的方式引發腸道中ssRNA誘導的5-HT合成。結腸灌注RNase A可抑制腸蠕動並增加骨量。這些發現表明腸道ssRNA是全身5-HT水平的主要決定因素，並揭示了ssRNA-Peizo1軸可作為骨和腸道疾病治療的潛在靶標。
據介紹，胃腸道腸嗜鉻細胞通過產生5-羥色胺來調控骨骼和腸道穩態。最近的研究表明，腸道微生物可調節5-HT水平。然而，確切的分子機制尚待探究。
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
Cell：《細胞》，創刊於1974年。隸屬於細胞出版社，最新IF：36.216