Interstitial fibrosis is significantly correlated with the progression of renal impairment for most causes of renal insufficiency. Transforming growth factor beta 1 (TGF-beta 1) and basic fibroblast growth factor (bFGF) are two of a group of profibrotic cytokines that have been associated with the development of renal interstitial fibrosis. We have previously demonstrated that alterations in D-glucose concentrations modulate the synthesis of TGF-beta 1 by human renal proximal tubular cells (HPTC) in vitro. The aim of the present study was to examine the influence of bFGF on TGF-beta 1 synthesis by HPTC in culture and to examine any modulation of this response by changes in ambient glucose concentration. Incubation of growth-arrested HPTC (72 hours in serum-free medium) with bFGF resulted in a dose-dependent increase in latent TGF-beta 1 secretion. Maximal release of TGF-beta 1 was seen at a bFGF dose of 50 ng/ml in cells incubated in 5 mM D-glucose (7.48+/-2.5 ng/ml, mean+/-SEM; n= 3; p= 0.04). This release of TGF-beta 1 in response to bFGF was unaffected by increasing the concentration of glucose in the culture media to 25 mM (7.76+/-1.3, mean+/-SEM; n= 3; p< 0.02). It was also unaffected by pretreatment of cells with either actinomycin-D or cycloheximide. TGF-beta 1 secretion was, however, inhibited in a dose-dependent manner by the exposure of cells to the microtubule-disrupting agent vinblastine, indicating that the generation of TGF-beta 1 was dependent on the secretion of preformed, stored TGF-beta 1. In a separate series of experiments, exposure of HPTC to TGF-beta 1 (10 ng/ml) led to the induction of bFGF mRNA, which was first apparent at 12 hours and reached maximal levels 24 hours after stimulation (normalized bFGF/alpha-actin mRNA ratio was 1.5 times that of the control). This increase in bFGF mRNA was accompanied by a time-dependent increase in bFGF protein production, which was maximal after 24 hours (19.83+/-12.7 pg/ml versus 2.49+/-0.34 pg/ml, mean+/-SEM, stimulated versus control; n= 3; p= 0.03). These findings demonstrate that bFGF stimulates the secretion of preformed, latent TGF-beta 1 by HPTC but does not induce de novo TGF-beta 1 gene transcription or TGF-beta 1 protein synthesis. We have also demonstrated a positive-feedback loop involving TGF-beta 1 and bFGF and postulate that this may be involved in the progressive nature of renal fibrosis in vivo.