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- Title
Role of membrane-bound heparin-binding epidermal growth factor-like growth factor (HB-EGF) in renal epithelial cell branching.
- Authors
Takemura, Tsukasa; Hino, Satoshi; Okada, Mituru; Murata, Yuka; Yanagida, Hidehiko; Ikeda, Masaru; Yoshioka, Kazuo; Harris, Raymond C
- Abstract
Background. The developing metanephros is characterized by growth and differentiation of the ureteric bud and the surrounding mesenchymal tissue. These processes can be influenced by several growth factors, including epidermal growth factor (EGF) and transforming growth factor-α (TGF-α). We examined whether another member of the EGF family of growth factors, heparin-binding epidermal growth factor (HB-EGF), might act as a morphogen in renal epithelial tubulogenesis. Methods. Expression of HB-EGF mRNA and immunoreactive protein were examined in fetal, neonatal and adult rat kidneys. For in vitro studies of tubulogenesis, a rat renal epithelial cell line (NRK52E) stably transfected with proHB-EGF (NRK[sup proHB-EGF) was treated with TPA for 30 minutes, washed with 2 mol/L NaCl to remove soluble HB-EGF trapped by cell surface heparan sulfate proteoglycan and replated onto plastic dishes in the absence of fetal calf serum. In further experiments, NRK[sup proHB-EGF] were suspended in a type I collagen gel in serumfree media. Results. Northern blot analysis indicated that HB-EGF was strongly expressed in embryonic rat kidney (embryonic days 18-20) and was still increased in the neonatal kidney (day 10), compared to the low basal levels in adult kidney. Immunohistochemical analysis confirmed that immunoreactive HB-EGF expression in the fetal rat kidney was localized predominantly to the ureteric bud. When NRK[sup proHB-EGF] were plated onto plastic substrata, they became progressively flattened and enlarged and exhibited filopoidia. By 10 hours after plating, NRK[sup proHB-EGF] began to migrate and subsequently developed cell-cell contact and fully established tubular-like structures. Immunoelectron microscopy revealed that the initial recovery of cellular proHBEGF was localized predominantly to areas of cell-cell attachment. No tubule-like structures were observed in similarly treated NRK52E cells transfected with the vector alone. In collagen gels,...
- Subjects
EPITHELIAL cells; KIDNEYS; EPIDERMAL growth factor; CYTOLOGY
- Publication
Kidney International, 2002, Vol 61, Issue 6, p1968
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.2002.00358.x