FGF-1 IN NORMAL AND REGENERATING KIDNEY - EXPRESSION IN MONONUCLEAR, INTERSTITIAL, AND REGENERATING EPITHELIAL-CELLS

The proximal tubule epithelium regenerates following nephrotoxic damag e. To determine the role of fibroblast growth factors (FGFs) in the re generation of rat proximal tubule epithelial (RPTE) cells, we investig ated proliferation, differentiation, and FGF-1 expression in vivo in r at kidney before and after nephrotoxic damage to the proximal tubule e pithelium caused by S-(1,1,2,2-tetrafluoroethyl)-L-cysteine administra tion. In undamaged kidneys, FGF-1 was expressed in distal tubule eleme nts, including cortical and medullary collecting ducts, as well as in blood vessels and glomeruli, but was absent in RPTE. One day after dam age, there was an increase in proliferation of surviving proximal tubu le epithelial cells and a coincident increase in FGF-1 expression in i nvading mononuclear cells. After this initial burst of proliferation, FGF-1 expression increased in poorly differentiated vimentin-positive regenerative epithelial cells, indicating that autocrine FGF-1 express ion in the regenerative epithelium is a later event in the regeneratio n process. FGF-1 staining persisted in foci of macrophages, interstiti al cells, and nephropathic tubules within areas of interstitial expans ion 2 wk after damage. We concluded that transient paracrine and autoc rine expression of FGF-1 could play mitogenic and/or morphogenic roles during tubular regeneration. Persistent expression in macrophages, fi broblasts, and nephropathic tubules may be associated with tubular deg eneration. FGF-1 expression may be an important contributor to both tu bular regeneration and degenerative disease following toxicant exposur e.