The long-term goals of this project concern a better understanding of the factors controlling the structure and function of the glomerular extracellular matrix. This is a highly specialized structure which is responsible for the maintenance of the glomerular filtration function. Diseases of the glomerulus are frequently associated with alterations in the structural integrity of the glomerular matrix or with the accumulation of abnormal quantities of this material. Glomerular mesangial cells have been found to secrete into culture medium an enzyme activity which can degrade a critical basement membrane component, type IV collagen. This enzyme activity was purified and characterized and found to be a type IV collagenase/gelatinase. Extensive structural analyses suggest that this enzyme may be unique and preliminary experiments using specific antibodies have localized this enzyme to the glomerular mesangium or normal and nephritianimals. It is proposed to continue the structural characterization of this enzyme by molecular cloning and sequence analysis and to determine the degree of expression of this enzyme in several models of nephritis. These expression studies will be performed at the immunohistochemical and in situ hybridization levels, using a new method developed in our laboratory. Finally, the polymerase chain reaction will be used to amplify sequences for related metalloproteases from the glomeruli of normal and nephritic animals, thereby considerably extending our current understanding of the types and patterns of proteolytic enzymes expressed by the intrinsic glomerular cells. This type of information could possibly lead to the development of highly specific inhibitors which could be used to block excessive activity of these enzymes in inflammatory states.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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Pathology A Study Section (PTHA)
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University of California San Francisco
Schools of Medicine
San Francisco
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Kim, Il Young; Kim, Sang Soo; Lee, Hye Won et al. (2018) The two isoforms of matrix metalloproteinase- 2 have distinct renal spatial and temporal distributions in murine models of types 1 and 2 diabetes mellitus. BMC Nephrol 19:248
Rhee, Harin; Han, Miyeun; Kim, Sang Soo et al. (2018) The expression of two isoforms of matrix metalloproteinase-2 in aged mouse models of diabetes mellitus and chronic kidney disease. Kidney Res Clin Pract 37:222-229
Baligand, Celine; Qin, Hecong; True-Yasaki, Aisha et al. (2017) Hyperpolarized 13 C magnetic resonance evaluation of renal ischemia reperfusion injury in a murine model. NMR Biomed 30:
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Lovett, David H; Cheng, Sunfa; Cape, Leslie et al. (2010) YB-1 alters MT1-MMP trafficking and stimulates MCF-7 breast tumor invasion and metastasis. Biochem Biophys Res Commun 398:482-8
Goldman, Shlomit; Lovett, David H; Shalev, Eliezer (2009) Mechanisms of matrix metalloproteinase-2 (mmp-2) transcriptional repression by progesterone in jar choriocarcinoma cells. Reprod Biol Endocrinol 7:41
Cheng, Sunfa; Pollock, Allan S; Mahimkar, Rajeev et al. (2006) Matrix metalloproteinase 2 and basement membrane integrity: a unifying mechanism for progressive renal injury. FASEB J 20:1898-900

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