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STRUCTURAL CHARACTERIZATION OF THE MESANGIAL CELL TYPE-IV COLLAGENASE AND ENHANCED EXPRESSION IN A MODEL OF IMMUNE COMPLEX-MEDIATED GLOMERULONEPHRITIS
Author(s): LOVETT DH, JOHNSON RJ, MARTI HP, MARTIN J, DAVIES M, COUSER WG
Source: AMERICAN JOURNAL OF PATHOLOGY    Volume: 141    Issue: 1    Pages: 85-98    Published: JUL 1992  
Times Cited: 133     References: 57     
Abstract: Secretion of glomerular cell-derived matrix metalloproteinases (MMPs) and their specific inhibitors, TIMP-1,2, may play an important role in the turnover of the glomerular extracellular matrix under basal and pathologic conditions. A 66-68 kd MMP secreted by cultured mesangial cells (MC) with activity against Type IV collagen and gelatin was purified and shown by amino-acid sequence analysis to be identical with a Type IV collagenase/gelatinase secreted by certain transformed tumor cell lines. The expression of the mesangial MMP in vivo was limited within the kidney to a small subset of the intrinsic glomerular mesangial cell population. After induction of acute anti-Thy 1.1 glomerulonephritis, there was a large increment in the number of Type IV collagenase-secreting MC, temporally coincident with the development of mesangial hypercellularity. The expression of the MMP inhibitor protein, TIMP-1, was not changed over this period. Ultrastructural studies localized the mesangial MMP to areas of evolving mesangiolysis and at sites of glomerular basement membrane disruption. Enhanced expression of the mesangial cell-derived Type IV collagenase may contribute to the evolution of glomerular injury in this model of immune complex-mediated glomerulonephritis or may be involved in the extensive matrix remodeling process that accompanies this form of glomerular injury.
Document Type: Article
Language: English
Reprint Address: LOVETT, DH (reprint author), VET ADM MED CTR, DEPT MED, DIV NEPHROL, MED SERV, 4150 CLEMENT ST, SAN FRANCISCO, CA 94121 USA
Addresses:
1. UNIV CALIF SAN FRANCISCO, SAN FRANCISCO, CA 94143 USA
2. UNIV WASHINGTON, DEPT MED, SEATTLE, WA 98195 USA
3. UNIV WALES COLL MED, CARDIFF CF4 4XN, S GLAM WALES
Publisher: AMER SOC INVESTIGATIVE PATHOLOGY, INC, 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993
Subject Category: Pathology
IDS Number: JC898
ISSN: 0002-9440
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