Angiotensin II increases connective tissue growth factor in the kidney.
Connective tissue growth factor (CTGF) has been described as a novel fibrotic mediator. CTGF is overexpressed in several kidney diseases and is induced by different factors involved in renal injury. Angiotensin II (AngII) participates in the pathogenesis of kidney damage, contributing to fibrosis; however, whether AngII regulates CTGF in the kidney has not been explored. Systemic infusion of AngII into normal rats for 3 days increased renal CTGF mRNA and protein levels. At day 7, AngII-infused rats presented overexpression of CTGF in glomeruli, tubuli, and renal arteries, as well as tubular injury and elevated fibronectin deposition. Only treatment with an AT(1) receptor antagonist, but not an AT(2), diminished CTGF and fibronectin overexpression and ameliorated tubular damage. In rats with immune complex nephritis, renal overexpression of CTGF was diminished by the ACE inhibitor quinapril, correlated with a diminution in fibrosis. In cultured renal cells (mesangial and tubular epithelial cells) AngII, via AT(1), increased CTGF mRNA and protein production, and a CTGF antisense oligonucleotide decreased AngII-induced fibronectin synthesis. Our data show that AngII regulates CTGF in the kidney and cultured in mesangial and tubular cells. This novel finding suggests that CTGF could be a mediator of the profibrogenic effects of AngII in the kidney.
Rupérez
Monica
M
Renal and Hypertension Unit, Fundación Jimenez Diaz, Universidad Autónoma de Madrid, Avenida Reyes Católicos, 228040 Madrid, Spain.
Ruiz-Ortega
Marta
M
Esteban
Vanesa
V
Lorenzo
Oscar
O
Mezzano
Sergio
S
Plaza
Juan Jose
JJ
Egido
Jesús
J
D000804:Angiotensin II / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D055513:Connective Tissue Growth Factor; D005260:Female; D017874:Immediate-Early Proteins / Q000187:drug effects* / Q000378:metabolism*; D007105:Immune Complex Diseases / Q000188:drug therapy / Q000473:pathology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D009393:Nephritis / Q000188:drug therapy / Q000276:immunology; D000077583:Quinapril; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044005:Tetrahydroisoquinolines / Q000494:pharmacology; D015854:Up-Regulation; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; C526316:CCN2 protein, rat; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D044005:Tetrahydroisoquinolines; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D055513:Connective Tissue Growth Factor; D000077583:Quinapril