維生素D3調控斑馬魚表皮離子細胞分化的機制

Abstract

淡水魚類生存在離子濃度多變的淡水環境中，因此淡水魚要如何適應離子激烈變動的環境對其是一大課題。維生素D3為一固醇類化合物，在生物體上也扮演賀爾蒙的角色，影響許多生理功能。前人研究指出維生素D3在哺乳動物的離子調節上扮演一定重要角色，然而在淡水魚類中，維生素D3是否在對不同離子的調節上扮演著重要的角色仍然不是很清楚。 本篇主要是探討維生素D3是否能夠影響魚類對不同離子的調節，此外魚類對離子調節的功能主要是由成魚的鰓或幼魚體表上的離子細胞所執行，因此本篇也進一步探討維生素D3是否能夠影響魚類離子細胞的增生或是分化進而影響離子吸收功能 。由於斑馬魚在分子生物學、發育學及基因體學資訊上的優勢，在本篇文章中以斑馬魚為模式動物進行探討維生素D3對魚類離子調節的影響。 在本文中發現浸泡維生素D3的斑馬魚仔魚，其體內鈉、鈣及氯離子含量皆顯著增加。此外與這些離子運輸相關的運輸蛋白基因表現也都會受到維生素D3浸泡的刺激。進一步研究維他命D3是經由何種方式影響斑馬魚離子調節，結果發現維生素D3經由影響離子細胞分化基因foxi3a的表現進而刺激斑馬魚仔魚的離子細胞分化，並且維生素D3可能經由vitamin D3-VDR signaling的途徑來調控離子吸收功能與細胞分化。 綜合本篇研究結果，維生素D3經由刺激離子細胞分化基因的表現，促使斑馬魚仔魚表皮幹細胞分化為離子細胞，因而影響離子細胞數量以及離子運輸蛋白的基因表現量，從而調控離子的吸收。

Fish face harsh and fluctuating ion composition in fresh water, therefore it is important that fish have to develop the regulatory mechanisms for ion homeostasis. Vitamin D3 is a group of fat-soluble secosteroids. It functions as a hormone and participates in many physiological reactions in animals. Vitamin D3 has been documented to be an endocrine of regulating ion uptake in mammals, however, the role of vitamin D3 on the different ions is still unclear in teleosts. In the present study, we focus on whether vitamin D3 controls the regulation of different ions. Since ionocytes primarily regulates ion transport in embryonic skin and/or adult gills of fish, we further explore whether vitamin D3 affects the proliferation or differentiation of ionocytes in teleosts. Plenty of genetic databases and mutants as well as the applicability of many molecular/cellular physiological approaches are advantages in using zebrafish (Danio rerio); a good model to investigate the molecular physiological mechanisms of epithelial ion uptake by vitamin D3 in teleosts. First, we observed whole-body content of Ca、Na and Cl as well as the expressions of ionocyte-related genes were up-regulated after vitamin D3 treatment. Subsequently, we further study the regulatory mechanism for ionocytes by vitamin D3. The data showed that vitamin D3 stimulated the differentiation of ionocytes by increasing the 4 expression of foxi3a, and the ionic regulation by vitamin D3 were mediated by vitamin D3-VDR signaling in zebrafish. Taken together, we demonstrated that vitamin D3controls the regulation of ionocytes differentiation through modulating activities of foxi3a to increase ionocyte densities, as well as the expressions of ion transporters and ultimately regulate the functions of ionocytes.