Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
Department of Life Science, National Taiwan University, Taipei, Taiwan.
Am J Physiol Regul Integr Comp Physiol. 2020 Apr 1;318(4):R751-R759. doi: 10.1152/ajpregu.00307.2019. Epub 2020 Feb 21.
Isotocin controls ion regulation through modulating the functions of ionocytes (also called mitochondria-rich cells or chloride cells). However, little is known about the upstream molecule of the isotocin system. Herein, we identify transient receptor potential vanilloid 4 (TRPV4), which regulates the mRNA and protein expressions of isotocin and affects ion regulation through the isotocin pathway. Double immunohistochemical results showed that TRPV4 is expressed in isotocinergic neurons in the hypothalamus of the adult zebrafish brain. To further elucidate the roles of TRPV4, we manipulated TRPV4 protein expression and evaluated its ionoregulatory functions in zebrafish embryos. TRPV4 gene knockdown with morpholino oligonucleotides decreased ionic contents (Na, Cl, and Ca) of whole larvae and the H-secreting function of larval skin of zebrafish. mRNA expressions of ionocyte-related transporters, including H-ATPase, the epithelial Ca channel, and the Na-Cl cotransporter, were also suppressed in morphants. Numbers of ionocytes (H-ATPase-rich cells and Na-K-ATPase-rich cells) and epidermal stem cells in zebrafish larval skin also decreased after knockdown. Our results showed that TRPV4 modulates ion balance through the isotocin pathway.
缩宫素通过调节离子细胞（也称为富含线粒体的细胞或氯离子细胞）的功能来控制离子调节。然而，关于缩宫素系统的上游分子知之甚少。本文中，我们鉴定出瞬时受体电位香草酸 4（TRPV4），它通过缩宫素途径调节缩宫素的 mRNA 和蛋白表达，并影响离子调节。双重免疫组织化学结果表明 TRPV4 在成年斑马鱼大脑下丘脑的缩宫素能神经元中表达。为了进一步阐明 TRPV4 的作用，我们操纵 TRPV4 蛋白表达并评估其在斑马鱼胚胎中的离子调节功能。用 morpholino 寡核苷酸敲低 TRPV4 基因会降低幼虫的离子含量（Na、Cl 和 Ca）和斑马鱼幼虫皮肤的 H 分泌功能。离子细胞相关转运蛋白（包括 H-ATPase、上皮 Ca 通道和 Na-Cl 共转运蛋白）的 mRNA 表达在 morphants 中也受到抑制。斑马鱼幼虫皮肤中的离子细胞（H-ATPase 丰富细胞和 Na-K-ATPase 丰富细胞）和表皮干细胞数量在 knockdown 后也减少。我们的结果表明 TRPV4 通过缩宫素途径调节离子平衡。
