Rajeswari Jithine Jayakumar, Vélez Emilio J, Unniappan Suraj
Laboratory of Integrative Neuroendocrinology, Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, S7N 5B4, Canada.
Laboratory of Integrative Neuroendocrinology, Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, S7N 5B4, Canada.
Growth Horm IGF Res. 2022 Apr;63:101456. doi: 10.1016/j.ghir.2022.101456. Epub 2022 Mar 10.
Phoenixin-20 (Pnx-20) is a bioactive peptide with endocrine-like actions in vertebrates. Recent studies suggest Pnx-20 promotes growth hormone/insulin-like growth factors (Gh/Igf) axis, an important endocrine regulator of growth in mammals and fish.
In this research, we determined whether Pnx-20 affects the different members of the Igf family, its binding proteins and receptors (Igf-system) in zebrafish liver and muscle.
In vivo administration of Pnx-20 downregulated igfs, igf receptors (igfrs) and igf binding protein (igfbp) 5 mRNA expression in the liver of male and female zebrafish at both 1 and 6 h post-intraperitoneal (IP) injection. Interestingly, this effect occurred at a relatively earlier timepoint in female zebrafish suggesting sex-specific differences in Pnx-20 action. Besides, either 6 or 24 h in vitro incubations with Pnx-20 downregulated the expression of all igfs, igfrs and igfbp5 mRNAs (except igf2a) analyzed in a zebrafish liver cell (ZFL) line. Moreover, siRNA-mediated knockdown of Pnx-20 upregulated all Igf-system mRNAs analyzed in ZFL cells. Together, these results (both in vivo and in vitro) revealed a general suppressive action for both endogenous and exogenous Pnx-20 on the hepatic Igf-system of zebrafish. In contrast, a general sex-specific upregulation of the Igf-system mRNAs analyzed was found in the muscle of Pnx-20 injected fish. Future research should explore the sex- and time-differences observed in the present study.
Collectively, this research shows that Pnx-20 is a tissue-specific regulator of the liver (suppressor) and muscle (stimulant) Igf signaling in both male and female zebrafish.
Phoenixin-20（Pnx-20）是一种在脊椎动物中具有类内分泌作用的生物活性肽。近期研究表明，Pnx-20可促进生长激素/胰岛素样生长因子（Gh/Igf）轴，这是哺乳动物和鱼类生长的重要内分泌调节因子。
在本研究中，我们确定了Pnx-20是否会影响斑马鱼肝脏和肌肉中Igf家族的不同成员、其结合蛋白和受体（Igf系统）。
腹腔注射（IP）后1小时和6小时，对雄性和雌性斑马鱼肝脏进行Pnx-20的体内给药，均下调了igfs、igf受体（igfrs）和igf结合蛋白（igfbp）5的mRNA表达。有趣的是，这种作用在雌性斑马鱼中出现的时间点相对较早，表明Pnx-20作用存在性别特异性差异。此外，在斑马鱼肝细胞（ZFL）系中，用Pnx-20进行6小时或24小时的体外孵育，下调了所有分析的igfs、igfrs和igfbp5 mRNA（igf2a除外）的表达。此外，siRNA介导的Pnx-20敲低上调了ZFL细胞中所有分析的Igf系统mRNA。总之，这些结果（体内和体外）揭示了内源性和外源性Pnx-20对斑马鱼肝脏Igf系统的普遍抑制作用。相比之下，在注射Pnx-20的鱼的肌肉中，所分析的Igf系统mRNA出现了普遍的性别特异性上调。未来的研究应探索本研究中观察到的性别和时间差异。
总体而言，本研究表明，Pnx-20是雄性和雌性斑马鱼肝脏（抑制剂）和肌肉（刺激剂）Igf信号传导的组织特异性调节因子。
