Inhibition of Notch pathway attenuates the progression of human immunodeficiency virus-associated nephropathy.

摘要: The Notch pathway is an evolutionarily conserved signaling cascade that critical in kidney development and has also been shown to play a pathogenetic role variety of diseases. We have previously the activated human immunodeficiency virus-associated nephropathy (HIVAN) as well rat model disease. In this study, we examined established Tg26 mouse HIVAN. components were distinctly upregulated kidneys these mice immortalized podocytes derived from mice. Notch1 Notch4 glomeruli, was expressed tubules. ligands Jagged1, Jagged2, Delta-like1, Delta-like 4 all tubules mice, but glomeruli showed minimal expression ligands. To examine potential for HIVAN, treated with GSIXX, gamma secretase inhibitor blocks signaling. Strikingly, GSIXX treatment resulted significant improvement both histological injury scores renal function. GSIXX-treated diminished podocyte proliferation dedifferentiation, cellular hallmarks Moreover, blocked vitro induced by HIV proteins Nef Tat. These studies suggest can promote HIVAN progression inhibition may be viable strategy