DOWN-REGULATION OF GLOMERULAR MATRIX METALLOPROTEINASE-2 GENE IN HUMAN NIDDM

Regulation of mesangial matrix deposition is a dynamic phenomenon invo lving synthetic and degradative processes. The latter involve a number of matrix metalloproteinases (MMP) and tissue inhibitors of matrix me talloproteinases (TIMP). Experimental studies suggest that mesangial m atrix degradation is inhibited in diabetic nephropathy, and that this phenomenon has a pathogenic role. The expression of genes for MMP2 and TIMP2 in human diabetic nephropathy was investigated. Reverse transcr iption polymerase chain reaction was carried out in microdissected glo meruli and tubulo-interstitium obtained from kidney biopsies. We studi ed 16 NIDDM patients, 5 patients with glomerulonephritis or chronic ki dney transplant rejection, and 5 normal control subjects. Albumin excr etion rate and renal histology for NIDDM patients were available. Cont rary to TIMP2 which was expressed both in tubulo-interstitium and glom eruli in almost all renal biopsies, MMP2 gene down-regulation was obse rved in glomeruli from all NIDDM patients, irrespective of the albumin excretion rate, and of renal histology. In contrast, this gene was ex pressed in biopsies from other subjects (chi.(2) = 20.6; p = 0.000), I n conclusion, this study demonstrates that: 1) in glomeruli of NIDDM p atients the MMP2 gene is down-regulated; 2) in biopsies of NIDDM patie nts the MMP2/TIMP2 pattern is peculiar for NIDDM; 3) the MMP2 gene dow n-regulation is observed in all NIDDM patients, irrespective of the le vel of albuminuria and of renal histology. MMP2 gene down-regulation s eems to be a molecular epiphenomenon of diabetes, rather than a marker of diabetic nephropathy.