Glomerulosclerosis occurs in a large number of human kidney diseases including diabetic nephropathy. It consists of the accumulation of extracellular matrix (ECM) within the glomerulus. Sclerosis may be mediated by dysregulation of both synthesis and degradation of ECM. A large family of matrix metalloproteinases as well as tissue inhibitors of metalloproteinase (TIMPs) play a role in the degradative process. Preliminary work reveals that: 1) normal mouse mesangial cells in culture secrete a 72 kD and a 92 kD gelatinase (type IV collagenase) as well as TIMP1; 2) mesangial cells derived form NOD mice and mice transgenic for bovine growth hormone (bGH) secrete only the 72 kD gelatinase; and 3) TIMP1 mRNA levels are modulated by cell density.
