Artikel
Inhibitor of differentiation Id2 is involved in the pathogenesis of angiotensin II-induced end-organ damage
Id2 (inhibitor of differentiation) in Angiotensin II induziertem Endorganschaden
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Veröffentlicht: | 8. August 2006 |
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Gliederung
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The helix-loop-helix transcription factor inhibitor of differentiation (Id) 2 has a pivotal role in determining cell lineage choice and differentiation. Id2 deficient mice (Id2-/-) lack Langerhans, splenic CD8 alpha + dendritic, and natural killer cells. Id2+/- mice appear to be normal. We observed earlier that dendritic and other immune cells are important mediators of angiotensin (Ang) II-induced renal damage. The aim of this study was to elucidate the role of the Id2 gene in cardiac and renal damage in transgenic mice over expressing the rat angiotensinogen gene (TGM). The mice are known to develop Ang II-induced cardiac hypertrophy and blood pressure increases. We mated Id2-/- with TGM. We compared TGMxId2+/- with TGMxId2-/- and the respective non-transgenic strains (WTxId2+/- and WTxId2-/-). Transgenic TGMxId2+/- showed significantly increased heart weight, cardiac hypertrophy index (5.4±0.2 mg/g), cardiac fibrosis, and left ventricular brain natriuretic peptide (BNP) expression. Albuminuria (235±40 µg/d), renal fibrosis, and cell infiltration were also significantly elevated. TGMxId2+/- showed media hypertrophy, extracellular matrix deposition, and tubular changes in the outer medulla. In contrast, cardiac hypertrophy (4.3±0.2 mg/g), albuminuria (25±10 µg/d), renal and cardiac fibrosis, macrophage and T-cell accumulation in the kidney and heart, were all significantly reduced in TGMxId2-/-. Albuminuria in WTxId2+/- and WTxId2-/- was 18±2 and 22±5 µg/d, respectively. No histopathological changes were observed in TGMxId2-/- and the non-transgenic groups. Our results demonstrate that Id2 plays a major role in the pathogenesis of Ang II-induced renal and cardiac damage.