The role of FGF-2 in renal fibrogenesis

Abstract

Basic fibroblast growth factor (FGF-2) is a pleiotropic cytokine which exerts its effects via four different high affinity receptors (FGFR-1 to -4) which function as protein tyrosine kinases. In the kidney, FGF-2 is expressed in epithelial cells already during fetal development. During later stages, expression of the cytokine can be found in distal tubular epithelial cells, glomerular cells and few interstitial cells. Expression in fibroblasts is robustly upregulated in chronic kidney scarring pointing to an important role in fibrogenesis. Functional studies have demonstrated that FGF-2 exerts mainly proliferative effects on a variety of renal cell types. In regard to fibrogenesis, the expression and induction of proliferation in interstitial fibroblasts may be the most important function. FGF-2 is one of the key factors contributing to autocrine fibroblast proliferation in post-inflammatory matrix synthesis. In addition, FGF-2 facilitates epithelial to mesenchymal transition of tubular epithelial cells contributing early to an increase of matrix producing cells. However, the cytokine does not contribute directly to extracellular matrix synthesis. Still, many aspects of FGF-2 in renal fibrogenesis remains to be evaluated.