title: Reciprocal expression of connexin 40 and 45 during phenotypical changes in renin-secreting cells.
abstract: Gap junctional coupling of renin-producing cells is of major functional importance for the control of renin synthesis and release. This study was designed to determine the relevance of the vascular gap junction protein connexin 45 (Cx45) for the control of renin expression and secretion. By crossbreeding mice which drive Cre recombinase under the control of the endogenous renin promoter with mice harboring floxed Cx45 gene alleles, we generated viable mice with a deletion of Cx45 in the renin cell lineage. These mice were normotensive, and renin cells in their kidneys were normal with regard to localization and number. Sodium deficiency induced typical recruitment of renin-producing cells along afferent arterioles, whereas sodium overload resulted in a decrease in the number of cells expressing renin. Regulation of renin secretion by perfusion pressure, catecholamines, and angiotensin II from isolated kidneys of mice with renin cell-specific deletion of Cx45 was normal. Analyzing Cx45 promoter activity in cells of the preglomerular arteriolar tree by using mice driving the reporter gene LacZ under the control of the Cx45 promoter revealed strong staining in smooth muscle cells of the media, whereas renin-expressing cells were almost devoid of LacZ staining. Conversely, renin-producing cells, but not vascular smooth muscle cells expressed the gap junction protein Cx40. These findings suggest that Cx45 plays no major functional role in renin-producing cells, probably because the expression of Cx45 is downregulated in these cells. Since renin-producing cells in the adult kidney can reversibly transform into vascular smooth muscle cells and vice versa, our findings on connexin expression indicate that these phenotype switches are paralleled by characteristic reciprocal changes in the transcriptional activity of Cx40 and Cx45 genes.
authors.affiliation: Institute of Physiology, University of Regensburg, Regensburg, Germany. birguel.kurt@vkl.uni-regensburg.de
authors.forename: Birguel
authors.initials: B
authors.lastname: Kurt
authors.forename: Lisa
authors.initials: L
authors.lastname: Kurtz
authors.forename: Maria L
authors.initials: ML
authors.lastname: Sequeira-Lopez
authors.forename: R Ariel
authors.initials: RA
authors.lastname: Gomez
authors.forename: Klaus
authors.initials: K
authors.lastname: Willecke
authors.forename: Charlotte
authors.initials: C
authors.lastname: Wagner
authors.forename: Armin
authors.initials: A
authors.lastname: Kurtz
mesh_terms: D000818:Animals; D017630:Connexins / Q000378:metabolism*; D019426:Integrases / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007763:Lac Operon / Q000502:physiology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D012083:Renin / Q000378:metabolism*; D017673:Sodium Chloride, Dietary / Q000494:pharmacology; D000097003:Gap Junction alpha-5 Protein
chemical_list: D017630:Connexins; D019426:Integrases; D012083:Renin; D017673:Sodium Chloride, Dietary; D000097003:Gap Junction alpha-5 Protein; C082920:connexin 45; C045073:Cre recombinase