Fibroblast growth factor-2 increases the renal recruitment and attachment of HIV-infected mononuclear cells to renal tubular epithelial cells |
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Authors: | Pingtao Tang Marina Jerebtsova Ronald Przygodzki Patricio E. Ray |
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Affiliation: | (1) Center for Genetic Medicine, Childrens Research Institute, Childrens National Medical Center, Room R-211, 3.5 Floor, 111 Michigan Ave. NW, Washington, DC 20010, USA;(2) Division of Nephrology, Childrens National Medical Center, Washington, DC, USA;(3) Division of Pathology, Childrens National Medical Center, Washington, DC, USA;(4) Department of Pediatrics, The George Washington University, Washington, DC, USA |
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Abstract: | The role of circulating growth factors in the pathogenesis of childhood HIV-1-associated nephropathy (HIVAN) is not clearly understood. In previous studies, we found a significant accumulation of fibroblast growth factor-2 (FGF-2) in the circulation and kidneys of children with HIVAN. The purpose of this study was to determine whether circulating FGF-2 may play a role in the pathogenesis of HIVAN by increasing the renal recruitment and attachment of HIV-infected mononuclear cells to renal epithelial cells. Using in vitro cell adhesion assays, we showed that FGF-2 increased the attachment of peripheral blood mononuclear cells (PBMCs) to fibronectin-coated tissue culture dishes by approximately threefold through a mechanism that involved the 5 integrin subunit. In addition, we found that FGF-2 induces a similar increase in the attachment of HIV-infected PBMCs and monocytes/macrophages to plastic tissue culture dishes and to monolayers of primary renal tubular epithelial cells harvested from the urine of HIV-infected children with renal disease. Finally, we injected 16 adult C57Bl6/J male mice with recombinant adenoviral vectors carrying either the LacZ gene or a secreted form of human FGF-2 (5×108 pfu/mouse) and demonstrated that high levels of circulating FGF-2 can increase the renal recruitment of circulating inflammatory cells and induce transient tubulointerstitial injury in vivo. These data suggest that FGF-2 may have an immunomodulatory role in the pathogenesis of HIVAN by recruiting HIV-infected cells in the kidney. |
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Keywords: | Fibroblast growth factor-2 (FGF-2) Renal tubular epithelial cells Attachment HIV-1 nephropathy HIV-infected mononuclear cells Renal disease |
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