An emerging body of data links sclerotic renal diseases and mesangial cell proliferation. These diseases may range from acute antibody medicated disorders to the sclerosis associated with 5/6th nephrectomy to even the most indolent and slowly progressive diseases such as diabetic nephropathy. In each of these disorders, there is evidence of mesangial cell proliferation and elaboration of abnormal amounts of extracellular matrix. Associated with these changes is the well known elaboration of TGF-B, and as they describe herein, the elaboration of the matrix metalloproteinase MMP-2 (the 72 kDa type IV collagenase). In vitro experiments with a highly proliferative mesangial cell line indicate that MMP-2 is a potent and very specific growth factor for mesangial cells. Its elimination through antisense techniques dramatically reverts these highly proliferative cells to quiescence. We have developed potent genetic means; catalytic ribozymes, and effective in vivo gene delivery techniques which allow us to study the effect of modulating MMP-2 production (and TGF-B receptor function) on the behavior of single identified mesangial cells in vivo. The hypothesis to be tested is that MMP-2 elaboration may be a central control point through which mesangial cell proliferation in vivo may be modulated. The means used are retroviral gene transfer to catalytic ribozymes to mesangial cells in vivo.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
Project #
Application #
Study Section
Pathology A Study Section (PTHA)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Northern California Institute Research & Education
San Francisco
United States
Zip Code
Mahimkar, Rajeev M; Visaya, Orvin; Pollock, Allan S et al. (2005) The disintegrin domain of ADAM9: a ligand for multiple beta1 renal integrins. Biochem J 385:461-8
Pollock, Allan S; Turck, Johanna; Lovett, David H (2003) The prodomain of interleukin 1alpha interacts with elements of the RNA processing apparatus and induces apoptosis in malignant cells. FASEB J 17:203-13
Mahimkar, R M; Baricos, W H; Visaya, O et al. (2000) Identification, cellular distribution and potential function of the metalloprotease-disintegrin MDC9 in the kidney. J Am Soc Nephrol 11:595-603
Jabrane-Ferrat, N; Pollock, A S; Goetzl, E J (2000) Inhibition of expression of the type I G protein-coupled receptor for vasoactive intestinal peptide (VPAC1) by hammerhead ribozymes. Biochemistry 39:9771-7
Tanney, D C; Feng, L; Pollock, A S et al. (1998) Regulated expression of matrix metalloproteinases and TIMP in nephrogenesis. Dev Dyn 213:121-9
Mertens, P R; Alfonso-Jaume, M A; Steinmann, K et al. (1998) A synergistic interaction of transcription factors AP2 and YB-1 regulates gelatinase A enhancer-dependent transcription. J Biol Chem 273:32957-65
Turck, J; Pollock, A S; Lovett, D H (1997) Gelatinase A is a glomerular mesangial cell growth and differentiation factor. Kidney Int 51:1397-400
Reddy, D; Pollock, A S; Clark, S A et al. (1997) Transfection and overexpression of the calcium binding protein calbindin-D28k results in a stimulatory effect on insulin synthesis in a rat beta cell line (RIN 1046-38). Proc Natl Acad Sci U S A 94:1961-6
Mertens, P R; Harendza, S; Pollock, A S et al. (1997) Glomerular mesangial cell-specific transactivation of matrix metalloproteinase 2 transcription is mediated by YB-1. J Biol Chem 272:22905-12
Turck, J; Pollock, A S; Lee, L K et al. (1996) Matrix metalloproteinase 2 (gelatinase A) regulates glomerular mesangial cell proliferation and differentiation. J Biol Chem 271:15074-83

Showing the most recent 10 out of 21 publications