title: Alteration of connexin expression is an early signal for chronic kidney disease.
abstract: Chronic kidney disease is promoted by a variety of factors that induce chronic inflammation and fibrosis. Inflammation and excessive scaring have been recently associated with disruptions of the gap junction-mediated intercellular communication. Nevertheless, little is known about alterations of the expression of gap junction proteins such as connexin (Cx) 43 and 37 in chronic renal disease. In this study, we investigated the expression of these two Cxs in the hypertensive RenTg mice, the anti-glomerular basement membrane glomerulonephritis, and the unilateral ureteral obstruction models, all leading to the development of chronic kidney disease in mice. Expression of Cx43 was almost negligible in the renal cortex of control mice. In contrast, Cx43 was markedly increased in the endothelium of peritubular and glomerular capillaries of the 3-mo-old RenTg mice, in the glomeruli of mice suffering from glomerulonephritis, and in the tubules after obstructive nephropathy. The Cx43 expression pattern was paralleled closely by that of the adhesion markers such as vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 as well as the inflammatory biomarker monocyte chemoattractant protein-1. In contrast, Cx37 that was abundantly expressed in the renal cortex of healthy mice was markedly decreased in the three experimental models. Interestingly, Cx43+/- mice showed restricted expression of VCAM-1 after 2 wk of obstructive nephropathy. These findings suggest the importance of Cxs as markers of chronic renal disease and indicate that these proteins may participate in the inflammatory process during the development of this pathology.
authors.affiliation: INSERM UMR S702, Batiment Recherche, Tenon Hospital, 4 rue de la Chine, 75020 Paris, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Toubas
authors.forename: Samantha
authors.initials: S
authors.lastname: Beck
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Pageaud
authors.forename: Anne-Cecile
authors.initials: AC
authors.lastname: Huby
authors.forename: Mouna
authors.initials: M
authors.lastname: Mael-Ainin
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Dussaule
authors.forename: Christos
authors.initials: C
authors.lastname: Chatziantoniou
authors.forename: Christos E
authors.initials: CE
authors.lastname: Chadjichristos
mesh_terms: D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers; D001794:Blood Pressure / Q000502:physiology; D001806:Blood Urea Nitrogen; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D018932:Chemokine CCL2 / Q000096:biosynthesis; D002908:Chronic Disease; D018031:Connexin 43 / Q000378:metabolism; D017630:Connexins / Q000096:biosynthesis*; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D007674:Kidney Diseases / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011507:Proteinuria / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D012083:Renin / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D018031:Connexin 43; D017630:Connexins; D012313:RNA; D012083:Renin