Matrix metalloproteinase-9 expression in renal biopsies of patients with HIV-associated nephropathy.
OBJECTIVE
The normal architecture and function of the kidney are maintained by a critical turnover of the extracellular matrix (ECM). Although increased synthesis of ECM leads to progression of renal failure, the role of degradation of ECM by metalloproteinases in progressive nephropathies is unclear. Recently, in an animal model of membranous glomerulonephritis (Heymann nephritis), visceral epithelial cell (VEC) injury has been found to rapidly increase matrix metalloproteinase-9 (MMP-9) synthesis by these cells during the period of maximal proteinuria. Because injury to glomerular VECs may be an important initiating factor in the pathogenesis of focal segmental glomerulosclerosis (FSGS), especially in HIV-associated nephropathy (HIVAN), we determined the expression of MMP-9 and its inhibitors in renal biopsies of patients with HIVAN.


METHODS
RNA was isolated from cortical renal tissue of 6 patients with HIVAN. Only those biopsies which displayed characteristic findings of HIVAN including collapsing FSGS, cystic dilatation of the tubules, and proliferation of VECs were used. As controls, we obtained renal cortical tissue from normal areas of kidneys removed due to malignancies. MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 mRNA expressions were determined using real-time quantitative reverse transcription-polymerase chain reaction. In all 6 patients with HIVAN, MMP-9 and TIMP-1 were overexpressed. We localized MMP-9 protein to the glomeruli with immunohistochemical detection.


CONCLUSIONS
MMP-9 is overexpressed in the glomeruli of patients with HIVAN and may be involved in the pathogenesis of the disease.
Ahuja
Tejinder S
TS
Department of Medicine, Division of Nephrology, University of Texas Medical Branch, Galveston, Tex, USA. tahuja@utmb.edu
Gopalani
Anisa
A
Davies
Peter
P
Ahuja
Harleen
H
D016263:AIDS-Associated Nephropathy / Q000201:enzymology* / Q000473:pathology*; D001706:Biopsy; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005921:Glomerulonephritis / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000201:enzymology / Q000473:pathology; D007678:Kidney Glomerulus / Q000201:enzymology* / Q000473:pathology*; D007680:Kidney Neoplasms / Q000201:enzymology / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis*; D016133:Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis
D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9