title: Dynamic expression of the sodium-vitamin C co-transporters, SVCT1 and SVCT2, during perinatal kidney development.
abstract: Isoform 1 of the sodium-vitamin C co-transporter (SVCT1) is expressed in the apical membrane of proximal tubule epithelial cells in adult human and mouse kidneys. This study is aimed at analyzing the expression and function of SVCTs during kidney development. RT-PCR and immunohistochemical analyses revealed that SVCT1 expression is increased progressively during postnatal kidney development. However, SVCT1 transcripts were barely detected, if not absent, in the embryonic kidney. Instead, the high-affinity transporter, isoform 2 (SVCT2), was strongly expressed in the developing kidney from E15; its expression decreased at postnatal stages. Immunohistochemical analyses showed a dynamic distribution of SVCT2 in epithelial cells during kidney development. In renal cortex tubular epithelial cells, intracellular distribution of SVCT2 was observed at E19 with distribution in the basolateral membrane at P1. In contrast, SVCT2 was localized to the apical and basolateral membranes between E17 and E19 in medullary kidney tubular cells but was distributed intracellularly at P1. In agreement with these findings, functional expression of SVCT2, but not SVCT1 was detected in human embryonic kidney-derived (HEK293) cells. In addition, kinetic analysis suggested that an ascorbate-dependent mechanism accounts for targeted SVCT2 expression in the developing kidney during medullary epithelial cell differentiation. However, during cortical tubular differentiation, SVCT1 was induced and localized to the apical membrane of tubular epithelial cells. SVCT2 showed a basolateral polarization only for the first days of postnatal life. These studies suggest that the uptake of vitamin C mediated by different SVCTs plays differential roles during the ontogeny of kidney tubular epithelial cells.
authors.affiliation: Departamento de Biología Celular, Centro de Microscopía Avanzada CMA BIO-BIO, Universidad de Concepción, Concepción, Chile. frnualart@udec.cl
authors.forename: Francisco
authors.initials: F
authors.lastname: Nualart
authors.forename: Tamara
authors.initials: T
authors.lastname: Castro
authors.forename: Marcela
authors.initials: M
authors.lastname: Low
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Henríquez
authors.forename: Karina
authors.initials: K
authors.lastname: Oyarce
authors.forename: Pedro
authors.initials: P
authors.lastname: Cisternas
authors.forename: Andrea
authors.initials: A
authors.lastname: García
authors.forename: Alejandro J
authors.initials: AJ
authors.lastname: Yáñez
authors.forename: Romina
authors.initials: R
authors.lastname: Bertinat
authors.forename: Viviana P
authors.initials: VP
authors.lastname: Montecinos
authors.forename: María Angeles
authors.initials: MA
authors.lastname: García-Robles
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured; D057809:HEK293 Cells; D006801:Humans; D007668:Kidney / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060347:Sodium-Coupled Vitamin C Transporters / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; C555162:SLC23A1 protein, human; C555163:SLC23A2 protein, human; C555164:Slc23a1 protein, mouse; C555165:Slc23a2 protein, mouse; D060347:Sodium-Coupled Vitamin C Transporters; D001205:Ascorbic Acid