HISTOLOGY AND HISTOPATHOLOGY

Cellular and Molecular Biology

 

Involvement of FGF and BMP family proteins and VEGF in early human kidney development

Dominko Carev1, Marijan Saraga2 and Mirna Saraga-Babic1

1Department of Anatomy, Histology and Embryology, School of Medicine,
University of Split, Split, Croatia and 2Department of Pediatrics, University Hospital Split, Split, Croatia.

Offprint requests to: Dominko Carev, Department of Anatomy, Histology and Embryology, School of Medicine, University of Split, Soltanska 2, 21000 Split, Croatia. e-mail: dominkocarev@yahoo.com


Summary. 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. Histol Histopathol 23, 853-862 (2008)

Key words: FGF, BMP, VEGF, Human kidney development

DOI: 10.14670/HH-23.853