TITLE

Precocious activation of genes of the renin-angiotensin system and the fibrogenic cascade in IgA glomerulonephritis

AUTHOR(S)
Del Prete, Dorella; Gambaro, Giovanni; Lupo, Antonio; Anglani, Franca; Brezzi, Brigida; Magistroni, Riccardo; Graziotto, Romina; Furci, Luciana; Modena, Francesca; Bernich, Patrizia; Albertazzi, Alberto; D'Angelo, Angela; Maschio, Giuseppe
PUB. DATE
July 2003
SOURCE
Kidney International;Jul2003, Vol. 64 Issue 1, p149
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Precocious activation of genes of the renin-angiotensin system and the fibrogenic cascade in IgA glomerulonephritis. Background. The renin-angiotensin system (RAS) seems to play a pivotal role in progression of immunoglobulin A (IgA) nephropathy (IgAN). Accordingly, in patients with IgAN a relationship between the RAS and the fibrogenic cascade triggered by transforming growth factor-β1 (TGF-β1) should be observed. This study was carried out to obtain deeper insight into the regulation of RAS and the interaction with TGF-β1 in the diseased kidney. Methods. Twenty renal biopsies from IgAN patients and five from renal cancer patients (controls) were analyzed in both microdissected glomerular and tubulointerstitial compartments by reverse transcription-polymerase chain reaction (RT-PCR). All patients had normal renal function. The expression of the following genes was determined: angiotensinogen (Agtg ), renin, angiotensin-converting enzyme (ACE ), angiotensin II (Ang II) type 1 and type II (AT1 and AT2 receptors ), TGF-β1 , collagen IV (Coll IV ), α-smooth muscle actin (α-SMA ). Quantitative data were confirmed for TGF-β1 and ACE genes by real-time PCR. Results. RAS genes were overexpressed in IgAN patients vs. control subjects. There was no difference between glomerular and tubulointerstitial RAS gene expression levels. On the contrary, the overactivation of fibrogenic cascade genes (TGF-β1 , Coll IV , α-SMA ) in the tubulointerstitium was observed (TGF-β1 , glomerular 0.14 ± 0.10 SD; tubulointerstial 0.34 ± 0.20; P = 0.000) (α-SMA , glomerular 0.08 ± 0.07; tubulointerstitial 0.35 ± 0.19; P = 0.000) (Coll IV , glomerular 0.12 ± 0.11; tubulointerstitial 0.22 ± 0.10; P = 0.03). This fibrogenic cascade seems to be triggered by RAS as indicated by statistically significant correlations between the expression of their respective genes. A direct relationship between the putative Ang II...
ACCESSION #
10131047

 

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