Opposing actions of TGFβ1 and FGF2 on growth, differentiation and extracellular matrix accumulation in prostatic stromal cells

TGF beta 1 and FGF2 are autocrine growth factors in prostatic stroma and are elevated in benign prostatic hyperplasia (BPH), a disease characterized by enlargement of the stromal compartment of the prostate. TGF beta 1 has a biphasic effect on proliferation of prostatic stromal cells, inducing proliferation at low doses (< 1 ng/ml), but inhibiting growth above 1 ng/ml. This study investigated the role of TGF beta 1 and FGF2 on growth factor bioavailability and extracellular matrix (ECM) accumulation synthesis in cultured prostatic stromal cells. Real-Time-PCR showed that TGF beta 1 expression is auto-inductive, whereas FGF2 is auto-repressive. FGF2 also induced TGF beta 1 secretion in the absence of increased TGF beta 1 mRNA expression. TGF beta 1 and FGF2 have opposing actions on Type 1 collagen expression, a finding confirmed by Western blotting. The bioavailability of TGF beta 1 regulated by FGF2 may represent part of a negative feedback mechanism controlling stromal growth, differentiation and ECM. Dysregulation of this pathway in favour of TGF beta 1 bioactivity may exacerbate BPH.