HUMAN GLOMERULI EXPRESS TIMP-1 MESSENGER-RNA AND TIMP-2 PROTEIN AND MESSENGER-RNA

Alterations in the balance between synthesis and degradation of extrac ellular matrix may result in glomerulosclerosis. The interaction betwe en metalloproteinases and their inhibitors presumably modulates the ra te of glomerular matrix degradation. We examined the gene expression o f tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2 in human glomeruli and TIMP-2 protein in tissue sections. Kidney tissue was obt ained from adults undergoing nephrectomy for renal tumor (n = 9) or bi opsy for nephrosis and renal failure (n = 1). Glomeruli were microdiss ected and subjected to reverse transcription. TIMP cDNAs were quantita ted by competitive polymerase chain reaction assays. Five nephrectomy specimens had normal glomeruli and four had diffuse glomerulosclerosis . TIMP-1 and TIMP-2 cDNA levels, detected in glomeruli from all patien ts, were increased fourfold and threefold, respectively, in patients w ith glomerulosclerosis. The elevated TIMP cDNA levels could not be att ributed to an increased number of glomerular cells. TIMP-2 protein was detected within normal and sclerotic glomeruli. In conclusion, both T IMP genes were expressed in normal glomeruli, and their level of expre ssion was increased in glomerulosclerosis associated with renal carcin oma, suggesting that expression of these inhibitors may correlate with the development of sclerosis.