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。一开始,测序深度便发展的一发而不可收拾,逐步开拓出属于自己的一片天空。
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myd88trif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
issuevolume: 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 myd88trif-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: 101016jcell202006022