Table2_The FGFR4 Homolog KIN-9 Regulates Lifespan and Stress Responses in Caenorhabditis elegans.XLSX

Fibroblast growth factor receptors (FGFRs) regulate diverse biological processes in eukaryotes. The nematode Caenorhabditis elegans is a good animal model for studying the roles of FGFR signaling and its mechanism of regulation. In this study, we report that KIN-9 is an FGFR homolog in C. elegans that plays essential roles in aging and stress response maintenance. kin-9 was discovered as a target of miR-246, a microRNA that is positively regulated by the Axin family member pry-1. We found that animals lacking kin-9 function were long-lived and resistant to chemically induced stress. Furthermore, they showed a reduced expression of endoplasmic reticulum unfolded protein response (ER-UPR) pathway genes, suggesting that kin-9 is required to maintain a normal ER-UPR. The analysis of GFP reporter-based expression in transgenic animals revealed that KIN-9 is localized in the intestine. Overall, our findings demonstrate that kin-9 is regulated by miR-246 and may function downstream of pry-1. This study prompts future investigations to understand the mechanism of miRNA-mediated FGFR function in maintaining aging and stress response processes.

成纤维细胞生长因子受体（Fibroblast growth factor receptors, FGFRs）可调控真核生物中的多种生物学过程。秀丽隐杆线虫（Caenorhabditis elegans）是研究FGFR信号通路作用及其调控机制的理想动物模型。本研究发现，KIN-9是秀丽隐杆线虫中的FGFR同源蛋白，在衰老与应激反应维持中发挥关键作用。kin-9最初被鉴定为miR-246的靶基因，而miR-246这一微小RNA（microRNA）的表达受Axin家族成员pry-1正向调控。我们观察到，kin-9功能缺失的线虫寿命更长，且对化学诱导的应激具有抗性。进一步分析显示，此类线虫的内质网未折叠蛋白反应（endoplasmic reticulum unfolded protein response, ER-UPR）通路基因表达水平降低，表明kin-9对于维持正常的ER-UPR通路功能是必需的。通过对转基因动物中基于绿色荧光蛋白报告基因（GFP reporter）的表达分析，我们发现KIN-9定位于肠道组织。综上，本研究结果证实kin-9受miR-246调控，并可能作用于pry-1的下游通路。本研究为阐明miRNA介导的FGFR功能在维持衰老与应激反应过程中的分子机制提供了新的研究方向。