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| ROLE OF THROMBOSPONDIN IN MESANGIAL CELL-GROWTH - POSSIBLE EXISTENCE OF AN AUTOCRINE FEEDBACK GROWTH CIRCUIT |
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| Author(s): MARINIDES GN, SUCHARD SJ, MOOKERJEE BK |
| Source: KIDNEY INTERNATIONAL Volume: 46 Issue: 2 Pages: 350-357 Published: AUG 1994 |
| Times Cited: 28 References: 40 |
| Abstract: Thrombospondin (TSP) is an extracellular matrix glycoprotein involved in mesangial cell (MC) adhesive and migratory function. We have studied the role of TSP in activation and proliferation of rat MC in serum-free media. TSP, in a concentration dependent manner (5 to 20 mu g/ml), caused an increase in thymidine uptake, first detectable at 28 hours and more prominent at 48 hours. This effect was inhibited by heparin and heparan sulfate. TSP induced epidermal growth factor (EGF) secretion and significantly augmented constitutive platelet-derived growth factor-AB (PDGF-AB) secretion by MC in a concentration dependent fashion. It did not, however, induce TGF-beta, IL-1, IL-6, IL-8, or TNF-alpha production. TSP had an additive effect with exogenous EGF and PDGF on thymidine uptake. Anti-PDGF neutralizing antibody eliminated the effect of TSP on MC growth. MC displayed a single class of heparin-inhibitable TSP binding sites (B-max 3.8 +/- 1.8 x 10(6)/cell, K-d = 80 +/- 29 nM). Based on these observations, we propose the existence of an autocrine positive feedback loop of MC proliferation involving TSP and growth factors, and regulated by heparan sulfate. |
| Document Type: Article |
| Language: English |
| Reprint Address: MARINIDES, GN (reprint author), SUNY BUFFALO, VET AFFAIRS MED CTR, DEPT MED, DIV NEPHROL, ROOM 1004B, 3495 BAILEY AVE, BUFFALO, NY 14215 USA |
Addresses:
1. SUNY BUFFALO, SCH MED, BUFFALO, NY USA
2. UNIV MICHIGAN, SCH MED, DEPT PEDIAT, HEMATOL ONCOL SECT, ANN ARBOR, MI USA |
| Publisher: BLACKWELL SCIENCE INC, 238 MAIN ST, CAMBRIDGE, MA 02142 |
| Subject Category: Urology & Nephrology |
| IDS Number: NX941 |
| ISSN: 0085-2538 |
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