Kolatsi, Maria; (1996) Hepatocyte growth factor and renal morphogenesis. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Hepatocyte growth factor/scatter factor (HGF/SF) is a growth factor which has a variety of effects on many target cells. Its effects have been reported to be mitogenic, motogenic and morphogenic. HGF/SF and its receptor MET, were studied in the developing and adult mouse kidney and in the developing human fetus. From investigating the early development of the mouse metanephros, HGF/SF was found to be expressed by renal mesenchymal cells while MET was expressed by both the ureteric bud and the mesenchyme. Conditionally- immortal cell lines derived from renal mesenchyme expressed either MET or both the ligand and receptor. Nephron formation and branching morphogenesis were disrupted when metanephric rudiments were grown in serum-free organ culture with neutralising anti-HGF/SF antibodies. Hence HGF/SF may have an autocrine and/or paracrine role in nephrogenesis. By studying the metanephros in more detail, I found that the vascular stalk of the glomerulus expressed the MET protein. Therefore I studied the role of HGF/SF and MET in individual mesangial cells derived from the adult kidney. Both HGF/SF and MET mRNA and protein were expressed by these mesangial cells and HGF/SF phosphorylated the MET receptor and caused the cells to acquire an elongated shape. Hence, HGF/SF may have an autocrine role in mesangial cells. From screening a number of human fetal organs taken from the first trimester of pregnancy, HGF/SF and MET were detected in organ systems which originate from mesenchymal-epithelial conversions and include the kidney, liver, lung and gut. HGF/SF and MET were also expressed in the chorionic villi of the placenta. Taken together these data imply that HGF/SF and MET may not only be important in mouse nephrogenesis but also in early human development.

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