Expression of fibroblast growth factors and their receptors in rat glomeruli

Abstract

Fibroblast growth factors (FGFs) regulate cell proliferation and differentiation, and are also important regulators of extracellular matrix. They are among the most potent angiogenic factors known. Evidence suggests the FGFs play a role in glomerular development and pathology. The aim of the present study was to determine whether FGF-1 (acidic FGF) and FGF-2 (basic FGF) and their receptors (FGFRs) were expressed in normal adult rat glomeruli, using reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. For RT-PCR studies, the kidneys of 200 g female Sprague-Dawley rats were perfused with buffer and glomeruli isolated using conventional sieving techniques followed by micropipetting. FGF-1 and FGF-2 were expressed in cortex and in glomeruli. All seven receptor isoforms assayed (FGFR1, 2 and 3 IIIb and IIIc splice variants, and FGFR4) were expressed in whole cortex. However, only the IIIc variants and FGFR4 were expressed in glomeruli. The relative levels of glomerular expression of these isoforms were determined using a semiquantitative RT-PCR assay using primers designed against three transmembrane regions; FGFR1 (100%); FGFR2 (0.1%); and FGFR4 (6%). Immunohistochemistry revealed specific immunostaining for all four FGFRs within glomeruli. The differential expression pattern of FGFR isoforms between glomeruli and whole cortex, and the mutually exclusive nature of the expression of IIIc but not IIIb isoforms within glomeruli, indicates that FGFR expression and thereby FGF activity is tightly regulated in glomeruli. These findings have important implications for the roles of the FGFs in glomerular health and disease.

Sprouty proteins regulate ureteric branching by coordinating reciprocal epithelialWnt11, mesenchymalGdnfand stromalFgf7signalling during kidney development

“…Fgfr1 was present in kidney mesenchymal cells regardless of their genetic status, as reported earlier (Dudley et al, 1999;Ford et al, 1997;Walshe and Mason, 2000), but its expression was lost in the more mature nephrons in the presence of human SPRY2, unlike the situation in the controls (Fig. 3, compare E with E′,E′′), suggesting that human SPRY2 expression has an influence on the maturation of the nephron, apparently owing to deregulated ureteric bud inductive signalling.…”

Expression of the fibroblast growth factor receptor 1–4 genes in glomeruli in anti-Thy1.1 mesangial proliferative glomerulonephritis

“…Expression of FGF2 and FGFR1 mRNA in normal rat kidneys has been detected using Northern blotting [7,30]. Expression of FGF and FGFR isoform mRNA in whole cortex and isolated glomeruli has also been demonstrated using the RT-PCR method [9]. We were unable to demonstrate mRNA for any of the FGFRs in normal rat glomeruli using an in situ hybridization method.…”

“…In previous studies, FGF2 has been found in mesangial areas, the glomerular basement membrane, glomerular epithelial cells, the basement membrane of Bowman's capsule, small arterial walls, and tubules of the normal kidney using the immunohistochemical method [7,26]. In an immunohistochemical study using frozen sections, expression of FGFRs 1-4 in normal glomeruli was observed [9]. It has recently been reported that the immunolocalization patterns for FGF2 differ according to the fixative or preparation technique used, and depending on the antibody specificity [3,12].…”

Role of Extracellular Matrix and Ras in Regulation of Glomerular Epithelial Cell Proliferation

“…36 Furthermore, rat glomeruli express various forms of FGFs and FGFRs. 37 In other types of glomerulonephritis, glomeruli may become infiltrated with inflammatory cells, eg, macrophages or platelets, which are sources of epithelial growth factors, including transforming growth factor-␣, EGF, and bFGF. 38,39 Production of HGF in intrinsic glomerular cells (eg, mesangial cells) might increase.…”