Anti-angiogenic compound (TNP-470) inhibits mesangial cell proliferation in vitro and in vivo

Kidney International
M HaraguchiJ Yoshikawa

Abstract

Growth factors, especially basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), and transforming growth factor-beta (TGF-beta) are known to play key roles in the pathogenesis of mesangial proliferative glomerulonephritis. TNP-470 (AGM-1470), a potent anti-angiogenic compound, has anti-growth factor properties and inhibits the activation of cyclin-dependent kinase (cdk) 2 and phosphorylation of RB protein. We investigated whether TNP-470 could suppress growth factor induced mesangial cell proliferation in vitro and experimental model of mesangial proliferative glomerulonephritis in vivo. TNP-470 inhibited potently PDGF- and bFGF-stimulated proliferation of rat mesangial cells in vitro (IC50 = 50 pg/ml). In anti-Thy 1.1 glomerulonephritis, high dose use of TNP-470 (20 mg/kg/day) markedly suppressed mesangial cell proliferation and mesangial matrix expansion on day 6; however, mesangiolysis remained. Low dose use of TNP-470 (10 mg/kg/day) moderately inhibited mesangial cell proliferation and mesangial matrix synthesis, and induced appropriate glomerular healing on day 14 in anti-Thy 1.1 glomerulonephritis. Thus, TNP-470 potently inhibits growth factor-induced proliferation of mesangial cells in vitro, and ...Continue Reading

References

Apr 1, 1992·The Journal of Experimental Medicine·D J PeacockE Brahn
Feb 14, 1991·Biochemical and Biophysical Research Communications·M KusakaJ Folkman
Apr 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·S J KimA B Roberts
Sep 13, 1991·Journal of Immunological Methods·N W RoehmA L Glasebrook
Jan 1, 1995·Kidney International·R J JohnsonW G Couser
Jun 1, 1994·Kidney International·R J Johnson
Sep 1, 1993·Kidney International·G GrandalianoH E Abboud
Apr 30, 1993·Biochemical and Biophysical Research Communications·M HanedaY Shigeta
Jan 1, 1993·Kidney International·H E Abboud

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Citations

Oct 26, 2000·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Y Q WangK Kaneda
Dec 13, 2005·Nephron. Experimental Nephrology·Peter J Nelson, Stuart J Shankland
Nov 4, 2000·Expert Opinion on Investigational Drugs·E A Kruger, W D Figg
Mar 19, 2004·Pathology International·Osamu MitaniHidekazu Shigematsu
Sep 29, 2020·Frontiers in Physiology·Afei ZhangYouwei Chen

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