Hechter Drake, Vahkal Brett, Tiede Tiana, Good Sara V
Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
Department of Biology, The University of Winnipeg, Winnipeg, Manitoba, Canada.
J Mol Endocrinol. 2022 May 12;69(1):R45-R62. doi: 10.1530/JME-21-0241.
There is no common consensus on the physiological role of insulin-like peptide 5 (INSL5) and its cognate receptor, relaxin family peptide receptor 4 (RXFP4). The experimental data for INSL5-RXFP4 expression and function point to a potential role of the peptide hormone and receptor pair in linking energy availability, homeostasis, and inflammation. In this review, we summarize studies on the INSL5-RXFP4 system and propose that the current findings from diverse experimental settings point broadly to a role as a protective energy sensor (PES). Specifically, we review the evidence that (1) INSL5-RXFP4 could regulate immune response by decreasing the production of proinflammatory cytokines and may be involved in the stress response via the HPA axis; (2) INSL5-RXFP4 may signal through sensory neurons on the vagus nerve, transmitting signals to the CNS; and (3) INSL5-RXFP4 could have local autocrine/paracrine roles within the intestinal tract and immune cells. Further investigation and clarification of these proposed roles of INSL5-RXFP4 may prove a greater physiological relevance for the pair and add to existing evidence of INSL5-RXFP4 role as a PES.
关于胰岛素样肽5（INSL5）及其同源受体松弛素家族肽受体4（RXFP4）的生理作用，目前尚无共识。INSL5 - RXFP4表达和功能的实验数据表明，该肽激素与受体对在连接能量供应、体内平衡和炎症方面可能发挥作用。在本综述中，我们总结了关于INSL5 - RXFP4系统的研究，并提出，来自不同实验环境的当前研究结果大致指向其作为一种保护能量传感器（PES）的作用。具体而言，我们回顾了以下证据：（1）INSL5 - RXFP4可通过减少促炎细胞因子的产生来调节免疫反应，并可能通过下丘脑 - 垂体 - 肾上腺（HPA）轴参与应激反应；（2）INSL5 - RXFP4可能通过迷走神经上的感觉神经元发出信号，将信号传递至中枢神经系统；（3）INSL5 - RXFP4可能在肠道和免疫细胞内具有局部自分泌/旁分泌作用。对INSL5 - RXFP4这些假定作用的进一步研究和阐明，可能会证明该肽激素与受体对具有更大的生理相关性，并为INSL5 - RXFP4作为PES的作用增添现有证据。
