Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Type of study
Language
Publication year range
1.
Am J Physiol Renal Physiol ; 291(2): F289-96, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16597610

ABSTRACT

Basic fibroblast growth factor (bFGF) is a heparin-binding growth factor that is accumulated in human dysplastic and cystic renal diseases. Previous studies have shown that bFGF can modulate the growth of developing renal tubules; however, its role in the pathogenesis of renal cyst formation is not clearly understood. Here, we tested the hypothesis that overexpression of bFGF in developing rodent kidneys induces cyst formation in vivo. We used two different adenoviral-mediated gene-transferring approaches to overexpress bFGF in developing rodent kidneys. Initially, metanephric kidney (MK) explants harvested from embryonic day 15 Sprague-Dawley rats were infected with adenoviral vectors (rAd) encoding human bFGF or LacZ genes and transplanted under the renal capsule of adult female rats. Subsequently, to determine whether bFGF could induce renal cysts in developing kidneys with an intact renal collecting system, we injected rAd-bFGF or LacZ vectors in the retroorbital plexus of newborn mice. Basic FGF induced a more efficient integration of the MK explants into the host kidneys and increased the vascularization and proliferation of developing tubules, leading to tubular dilatation and rapid formation of renal cysts. In addition, we successfully expressed human bFGF in the kidney of newborn mice in vivo and induced tubular dilatation and renal cysts. In contrast, mice injected with rAd-lacZ did not develop tubular dilatation or renal cysts. To the best of our knowledge, these experiments show for the first time that overexpression of bFGF in developing rodent kidneys can induce the formation of renal cysts in vivo.


Subject(s)
Fibroblast Growth Factor 2/physiology , Kidney Diseases, Cystic/physiopathology , Kidney/growth & development , Kidney/physiology , Adenoviridae/genetics , Animals , Animals, Newborn/physiology , Cell Proliferation , Female , Fibroblast Growth Factor 2/genetics , Gene Expression Regulation, Developmental/physiology , Gene Transfer Techniques , Genetic Vectors/genetics , Humans , Kidney/chemistry , Kidney/cytology , Kidney Diseases, Cystic/etiology , Kidney Tubules, Collecting/chemistry , Kidney Tubules, Collecting/cytology , Kidney Tubules, Collecting/growth & development , Kidney Tubules, Collecting/physiology , Mice , Mice, Inbred C57BL , Organ Culture Techniques , RNA, Messenger/analysis , RNA, Messenger/genetics , Rats , Rats, Sprague-Dawley
2.
Kidney Int ; 61(1 Suppl): S16-23, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11841607

ABSTRACT

BACKGROUND: The expression of foreign genes into renal glomerular cells holds enormous potential to modulate the outcome of renal diseases. Recombinant adenoviruses (rAds) are promising gene transfer vectors because they have the ability to infect a wide range of nondividing cells. However, despite the fact that renal glomeruli are easily accessible via the renal circulation, adenovirus-mediated gene transfer into rodent glomeruli has been problematic. Here, we described our experience using rAd vectors to express foreign genes in rodent renal glomeruli in vivo and in cultured human renal glomerular cells. METHODS: We developed two techniques--the "portal clamping" and "prolonged renal infusion"--to infect mouse and rat renal glomeruli in vivo, respectively. We used E-1-deleted rAd vectors carrying the lacZ gene encoding beta-galactosidase (Ad. CBlacZ) under the control of the cytomegalovirus enhancer and chicken beta-actin promoter. Cultured human renal glomerular podocytes, endothelial and mesangial cells were grown following standard techniques. Transgene expression was evaluated by doing beta-galactosidase staining and reverse transcription-polymerase chain reaction studies. RESULTS: We found that both a prolonged exposure and a high concentration of circulating adenoviral vectors were required to achieve efficient gene transfer to renal glomerular cells in rodents. The virus-mediated transgene expression in renal glomeruli lasted for at least 42 days in mice and 21 days in rats without causing significant renal injury. CONCLUSIONS: These data demonstrate the feasibility of using rAd vectors as a tool to express foreign genes in rodent renal glomerular cells and suggest that all types of human renal glomerular cells are equally susceptible to rAd infection.


Subject(s)
Adenoviridae , Gene Transfer Techniques , Kidney Glomerulus/virology , Animals , Cells, Cultured , Constriction , Humans , Infusions, Intra-Arterial , Kidney Glomerulus/cytology , Mice , Rats
SELECTION OF CITATIONS
SEARCH DETAIL
...