Involvement of FGF and BMP family proteins and VEGF in early human kidney development.
The spatial and temporal pattern of the appearance of the fibroblast growth factor proteins (FGF-8 and FGF-10), the bone morphogenetic proteins (BMP-2/4 subfamily and BMP-7) and the vascular endothelial growth factor protein (VEGF) was investigated in the human mesonephros and metanephros of the 5-9 week-old conceptuses. In the mesonephros, both FGF's and BMP's were found in all structures and their expression slightly decreased in the early fetal period. VEGF positivity appeared in all mesonephric structures, and increased in the fetal period coincidently with formation of the mesonephric blood vessel network. In the metanephros, FGF-8 first appeared only in the metanephric mesenchyme, but from the 7th week on, its reactivity increased and spread to other metanephric structures. FGF-10 positive cells appeared in all metanephric structures already in the 5th week, and slightly intensified with progression of development. Cell survival and nephrogenesis in the permanent kidney might be associated with the appearance of both growth factors. Both BMP-2/4 and BMP-7 displayed a similar pattern of reactivity in all metanephric structures, and their reactivity intensified with advancing development. Alterations in their pattern of appearance might lead to the formation of small and dysplastic kidneys. Already in the earliest developmental stages, VEGF protein appeared in all metanephric structures. At later stages, VEGF showed more intense reaction in the collecting system than in the differentiating nephrons and interstitium. Due to VEGF involvement in vasculogenesis and angiogenesis, abnormal VEGF appearance might lead to impaired formation of the blood vessel network in the human permanent kidney.
Carev
Dominko
D
Department of Anatomy, Histology and Embryology, School of Medicine, University of Split, Split, Croatia. dominkocarev@yahoo.com
Saraga
Marijan
M
Saraga-Babic
Mirna
M
D015415:Biomarkers / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D047108:Embryonic Development; D051526:Fibroblast Growth Factor 10 / Q000378:metabolism*; D051524:Fibroblast Growth Factor 8 / Q000378:metabolism*; D005865:Gestational Age; D006801:Humans; D007668:Kidney / Q000196:embryology* / Q000378:metabolism; D008650:Mesonephros / Q000098:blood supply / Q000196:embryology / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
C525718:BMP2 protein, human; C525809:BMP4 protein, human; C525819:BMP7 protein, human; D015415:Biomarkers; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; C496463:FGF10 protein, human; C496456:FGF8 protein, human; D051526:Fibroblast Growth Factor 10; D016212:Transforming Growth Factor beta; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051524:Fibroblast Growth Factor 8