Endothelial-Specific Deletion of CD146 Protects Against Experimental Glomerulonephritis in Mice
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Endothelial-Specific Deletion of CD146 Protects Against Experimental Glomerulonephritis in Mice. / Abed, Ahmed; Leroyer, Aurélie S; Kavvadas, Panagiotis; Authier, Florence; Bachelier, Richard; Foucault-Bertaud, Alexandrine; Bardin, Nathalie; Cohen, Clemens D; Lindenmeyer, Maja T; Genest, Magali; Joshkon, Ahmad; Jourde-Chiche, Noémie; Burtey, Stéphane; Blot-Chabaud, Marcel; Dignat-George, Françoise; Chadjichristos, Christos E.
in: HYPERTENSION, Jahrgang 77, Nr. 4, 04.2021, S. 1260-1272.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Endothelial-Specific Deletion of CD146 Protects Against Experimental Glomerulonephritis in Mice
AU - Abed, Ahmed
AU - Leroyer, Aurélie S
AU - Kavvadas, Panagiotis
AU - Authier, Florence
AU - Bachelier, Richard
AU - Foucault-Bertaud, Alexandrine
AU - Bardin, Nathalie
AU - Cohen, Clemens D
AU - Lindenmeyer, Maja T
AU - Genest, Magali
AU - Joshkon, Ahmad
AU - Jourde-Chiche, Noémie
AU - Burtey, Stéphane
AU - Blot-Chabaud, Marcel
AU - Dignat-George, Françoise
AU - Chadjichristos, Christos E
PY - 2021/4
Y1 - 2021/4
N2 - CD146 is an endothelial junctional adhesion molecule, which expression is increased in human glomerular diseases. However, the pathological significance of this overexpression remains unknown. Induction of glomerulonephritis in mice, by using nephrotoxic serum, showed that CD146 expression was highly induced within damaged glomeruli and was associated with renal inflammation and fibrosis. Interestingly, 2 weeks after glomerulonephritis induction, CD146 knockout mice showed preserved renal function as proteinuria and blood urea nitrogen levels were significantly lower compared with wild-type littermates. Furthermore, renal structure was considerably conserved, since crescents formation, tubular dilation, monocyte and lymphocyte infiltration, and interstitial renal fibrosis were highly reduced. Colocalization with markers for different types of glomerular cells showed that CD146 expression was mainly increased within the injured endothelium of the glomerular tuft. Consequently, we generated a new transgenic strain in which CD146 was specifically deleted in the vascular endothelium. Similarly to CD146 knockout, these mice showed preservation of renal structure and function after the induction of glomerulonephritis compared with wild-type animals. These data show that endothelial CD146 plays a major role in glomerulonephritis and may represent a novel therapeutic target to reduce glomerular damage and the progression of renal disease.
AB - CD146 is an endothelial junctional adhesion molecule, which expression is increased in human glomerular diseases. However, the pathological significance of this overexpression remains unknown. Induction of glomerulonephritis in mice, by using nephrotoxic serum, showed that CD146 expression was highly induced within damaged glomeruli and was associated with renal inflammation and fibrosis. Interestingly, 2 weeks after glomerulonephritis induction, CD146 knockout mice showed preserved renal function as proteinuria and blood urea nitrogen levels were significantly lower compared with wild-type littermates. Furthermore, renal structure was considerably conserved, since crescents formation, tubular dilation, monocyte and lymphocyte infiltration, and interstitial renal fibrosis were highly reduced. Colocalization with markers for different types of glomerular cells showed that CD146 expression was mainly increased within the injured endothelium of the glomerular tuft. Consequently, we generated a new transgenic strain in which CD146 was specifically deleted in the vascular endothelium. Similarly to CD146 knockout, these mice showed preservation of renal structure and function after the induction of glomerulonephritis compared with wild-type animals. These data show that endothelial CD146 plays a major role in glomerulonephritis and may represent a novel therapeutic target to reduce glomerular damage and the progression of renal disease.
KW - Animals
KW - CD146 Antigen/genetics
KW - Disease Models, Animal
KW - Drug Discovery
KW - Endothelial Cells/metabolism
KW - Fibrosis/metabolism
KW - Gene Knockout Techniques/methods
KW - Glomerulonephritis/immunology
KW - Inflammation/metabolism
KW - Intercellular Junctions/immunology
KW - Kidney Glomerulus/immunology
KW - Mice
KW - Up-Regulation
U2 - 10.1161/HYPERTENSIONAHA.119.14176
DO - 10.1161/HYPERTENSIONAHA.119.14176
M3 - SCORING: Journal article
C2 - 33689459
VL - 77
SP - 1260
EP - 1272
JO - HYPERTENSION
JF - HYPERTENSION
SN - 0194-911X
IS - 4
ER -