Pingtao Tang
Children’s National Health System, USA
Title: HIV Tat-induced activation of the ERK pathway and HIV gene expression precede the proliferation and dedifferentiation of renal cells in HIV-Tg26 mice
Biography
Biography: Pingtao Tang
Abstract
Introduction & Objective: The HIV-Tat protein is a powerful activator of HIV transcription, but can also be released by infected cells and induce the dysregulation and proliferation of cultured human podocytes not infected with HIV-1. However, it is unclear whether HIV-Tat can induce proliferation and de-differentiation of podocytes and activation of the ERK pathway thereby enhance renal injury of effect of HIV-1 gene in vivo. To determine whether HIV-Tat can induce the renal expression of HIV-1 gene and the proliferation and de-differentiation of glomerular epithelial cells and activation of ERK pathway thereby effect of renal injury in HIV-Transgenic (HIV-Tg26) mice.
Method: rAd-Tat and LacZ control vectors (2×109) were expressed in renal glomeruli of WT and HIV-Tg 26 young mice without pre-existing renal disease. Mice were sacrificed at 7 days and 35 days. The renal expression of HIV-genes, nephrin, synaptopodin, WT-1, cyclin D-1, FGF-2, VEGF and signaling pathways that modulate the growth of glomerular epithelial cells was assessed by RT-PCR, Immunohiostochemistry and Western blots.
Result & Conclusion: At seven days, rAd-Tat induced the renal expression of HIV envelope gene in HIV-Tg26. This change was associated with activation of the ERK pathway and up-regulation of FGF-2 and VEGF that preceded the proliferation and de-differentiation (down regulation of nephrin, synaptopodin and WT-1) of renal glomerular epithelial cells. rAd-Tat reduced activate caspase-3 and apoptosis of renal cells at seven days. It also preceded the down regulation of cyclin D1, WT-1, nephrin, synaptopodin and the proliferation of renal glomerular epithelial cells at 35 days. rAd-Tat induces the expression of HIV-1 gene (env) in the kidney of HIV-Tg26 mice. This change was associated with activation of the ERK pathway and up regulation of FGF-2 and VEGF that preceded the development of proliferative changes in renal epithelial cells and de-differentiation of podocytes in HIV-Tg26 mice.