Increased expression of fibroblast growth factors in segmental renal dysplasia

Abstract

 Renal dysplasia (RD) is a disorganized development of renal parenchyma that results in a deficit of functional renal tissue. Dysplastic renal tissue is characterized by primitive tubular epithelium associated with increased mesenchyme. Several polypeptide growth factors (GF), which interact with target cells through a cell-surface membrane receptor, have been reported to be involved in the regulation of urothelial cell growth in normal and neoplastic states. Recent reports have demonstrated that basic fibroblast GF (bFGF, FGF-2) is a mitogen for renal proximal-tubule epithelial cells. Keratinocyte GF (KGF, FGF-7), which belongs to the FGF family, is believed to be a paracrine mediator of epithelial-cell proliferation. The aim of this study was to investigate the immunoactivity of bFGF and KGF and their receptors in the dysplastic kidney in order to further understand the pathogenesis of RD. Specimens of dysplastic upper poles of duplex kidneys were surgically resected from ten patients. Age-matched control material included six kidney specimens taken at autopsy from patients without evidence of urologic disease. Indirect immunohistochemistry was performed using the Strept-ABC method with four antibodies: bFGF, KGF, FGF receptor (flg), and KGF receptor (bek). There was absent or weak bFGF, KGF, flg, and bek immunoreactivity in normal kidneys. In the dysplastic kidneys, there was strong immunoreactivity of bFGF and KGF and their receptors in the epithelium of primitive tubules. Increased local expression of bFGF and KGF and their receptors in primitive tubules suggests that bFGF and KGF may play an important role in the development of RD.