Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation
Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation
复制标题
DOI：
10.1073/pnas.1215927110
复制
发表时间：
2013-03-12
影响因子：
11.1
通讯作者：
Caplan, Michael J.
中科院分区：
文献类型：
--
作者：
Pluznick, Jennifer L.;Protzko, Ryan J.;Caplan, Michael J.
嗅觉受体是G蛋白偶联受体，其介导嗅觉化学感觉并在其他组织中充当化学传感器。我们发现，Olfr 78，在肾脏中表达的嗅觉受体，响应短链脂肪酸（SCFAs）。Olfr 78在肾肾小球器中表达，在那里它响应于SCFA介导肾素分泌。此外，Olfr 78和G蛋白偶联受体41（Gpr41）（另一种SCFA受体）均在小阻力血管的平滑肌细胞中表达。丙酸盐是一种SCFA，可诱导离体血管舒张，在野生型小鼠中产生急性肿胀反应。这种作用通过Olfr78和Gpr41表达的破坏而被差异调节。SCFA是肠道微生物群发酵的最终产物，并被吸收到循环中。抗生素治疗降低了Olfr78基因敲除小鼠肠道微生物群的生物量并升高了血压。我们得出结论，肠道微生物群产生的SCFAs通过Olfr78和Gpr41调节血压。
Olfactory receptors are G protein-coupled receptors that mediate olfactory chemosensation and serve as chemosensors in other tissues. We find that Olfr78, an olfactory receptor expressed in the kidney, responds to short chain fatty acids (SCFAs). Olfr78 is expressed in the renal juxtaglomerular apparatus, where it mediates renin secretion in response to SCFAs. In addition, both Olfr78 and G protein-coupled receptor 41 (Gpr41), another SCFA receptor, are expressed in smooth muscle cells of small resistance vessels. Propionate, a SCFA shown to induce vasodilation ex vivo, produces an acute hypotensive response in wild-type mice. This effect is differentially modulated by disruption of Olfr78 and Gpr41 expression. SCFAs are end products of fermentation by the gut microbiota and are absorbed into the circulation. Antibiotic treatment reduces the biomass of the gut microbiota and elevates blood pressure in Olfr78 knockout mice. We conclude that SCFAs produced by the gut microbiota modulate blood pressure via Olfr78 and Gpr41.