Abstract 1946 Nephrology Platform, Sunday, 5/2

Full elucidation of the role of growth factor receptors in human renal development relies heavily on analogy with other animal species, in which the full time course of the expression of such factors can be mapped throughout fetal development. We have previously shown that the growth factor receptor Met is involved in the early stages of mouse kidney development. Met induces mesenchymal to epithelial cell conversion in embryonic cells. Moreover, it is highly expressed in kidney cells undergoing mesenchymal-epithelial conversion (Science 1994; 263: 98-101). Recently, we transplanted human fetal kidney tissue under the kidney capsule of immunodeficient rats and showed rapid growth as well as cellular differentiation and maturation over a long time span (Transplantation 1997; 64:1550-8). We now report evaluation of Met expression in our model.

Human fetal grafts originating from 12-week-old fetuses were harvested at 10, 21, 28, 56, and 112 days following implantation.

Histology, immunohistochemistry and confocal laser scanning microscopy (CLSM) were used to examine Met involvement in embryonic kidney development. Examination of the histological sections revealed that early figures (ureteric buds, comma- and S-shape bodies) in the human embryonic kidneys were abundant at 10 and 28 days but rare at 56 and 112 days. Early after implantation (10,28 days) the highest expression of Met were observed in the branches of the ureteric buds, while in primitive nephrons such as S and comma shaped body staining (primarily luminal) was much weaker. 56 and 112 days after implantation, grafts showed increasing numbers of differentiated tubular structures and vascularized maturing glomeruli, and the earlier figures could hardly be detected. These stages of the histologic transformation were associated with remarkable up-regulation of Met expression. Met staining was observed both on basal and luminal surfaces of mature epithelia of evolving proximal, distal and collecting tubules. Little staining, located in bowman's capsule, was found in developing human glomeruli. Staining of human adult kidney revealed a lower level of Met in the tubules compared to that found in the fetal grafts.

Our results suggest an important role for Met in tubulogenesis occurring in long-term human fetal renal transplants and further demonstrates the usefulness of our model in studying human nephrogenesis.