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Extracellular actin impairs glomerular capillary repair in experimental mesangioproliferative glomerulonephritis

Janssen, Ulf
Eitner, Frank
Kunter, Uta
Ostendorf, Tammo
Wolf, Gunter
Kerjaschki, Dontscho
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Published in Nephron Experimental Nephrology. 2003, vol. 93, no. 4, p. e158-167
Abstract Exogenous administration of actin prevents tumour growth in mice by specifically antagonizing angiogenin, a potent inducer of neovascularization. To investigate whether the angiogenin/actin system is also of importance in renal disease, we examined the effect of actin during glomerular capillary repair in anti-Thy-1.1 mesangioproliferative glomerulonephritis. Male Wistar rats were injected intravenously with actin, a control protein, i.e. albumin, or vehicle alone at 8, 16, 24, 32, 40 and 48 h after disease induction. On day 8, actin-treated rats showed significantly more microaneurysms and persistent mesangiolysis as compared to both control groups. This was associated with increased proteinuria in actin-treated rats. Moreover, actin-treated rats showed increased counts of glomerular macrophages (+40%) and polymorphonuclear leukocytes (+100%) on day 3 as well as a decrease in glomerular endothelial area on days 3 and 8. However, no difference in early glomerular endothelial as well as non-endothelial cell proliferation was noted in actin-treated rats as compared to controls. Actin treatment had no apparent influence on mesangial cell activation (i.e. de novo expression of alpha-smooth muscle actin) or glomerular accumulation of fibronectin or type IV collagen. Additional in vitro studies demonstrated that extracellular actin inhibits the angiogenin but not VEGF(165)-induced proliferation of (glomerular) endothelial cells. Moreover, actin inhibited other, yet unidentified, serum-derived angiogenic factors. In conclusion, exogenous actin impairs glomerular capillary repair in experimental mesangioproliferative glomerulonephritis possibly due to interference with angiogenic factors such as angiogenin. Our combined in vivo and in vitro observations suggest that the release of intracellular actin during mesangiolysis is an endogenous pathway by which glomerular capillary damage is augmented.
Keywords Actins/administration & dosage/ physiologyAnimalsAorta/chemistryApoptosis/drug effectsCapillaries/physiopathologyCattleCell Division/drug effectsCells, CulturedDose-Response Relationship, DrugEndothelium, Vascular/cytology/drug effectsExtracellular Matrix/drug effects/pathologyGlomerular Mesangium/ blood supply/drug effects/metabolism/pathologyGlomerulonephritis, Membranoproliferative/ metabolism/physiopathologyHumansInjections, IntravenousKidney Glomerulus/ blood supply/drug effects/physiopathologyLeukocytes/drug effects/metabolismMaleMuscle, Smooth/chemistryPilot ProjectsRatsRats, Wistar
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PMID: 12759577
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