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      TGF-Alpha mRNA Expression in Renal Organogenesis: A Study in Rat and Human Embryos

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          The peptides belonging to the epidermal growth factor (EGF) family play a significant role in kidney development by binding the EGF receptor. Transforming growth factor-α (TGFα), a member of this family, is thought to be the fetal ligand of the EGF receptor. The present study aims to localize the TGFα transcripts in rat and human embryonic kidneys using a nonradioactive in situ hybridization method on paraffin-embedded embryonic samples. The results obtained in this study, beside demonstrating the usefulness of the nonradioactive technique for the detection of TGFα mRNA in paraffin sections, allowed TGFα-producing cells to be seen in developing kidneys. TGFα mRNA and its respective peptide were found in the primitive mesonephric structures and within metanephric blastema and ureteric bud cells. The presence of the TGFα gene transcript in the developing rat and human kidney suggests that the TGFα peptide is of embryonic origin and that it may contribute to renal organogenetic processes together with other growth factors.

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          Immunohistochemical localization of the epidermal growth factor, transforming growth factor alpha, and their receptor in the human mesonephros and metanephros.

          The distribution of epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha), and EGF/TGF alpha receptor were studied by means of immunohistochemical methods starting from the very early stages of human embryonic kidney development. Mesonephros and metanephros were examined in order to detect immunoreactive staining in serial sectioned embryos and fetal kidneys. Anti-EGF immunoprecipitates were found in the S-shaped mesonephric vesicles of 6-week old embryos as well as in the mesonephric duct albeit with a lower degree of reactivity. Intense reactivity was observed in the metanephros within the blastemic caps of the same gestational period; the reaction was weaker within the ureteric bud branches. Bowman's capsule, proximal tubules, and collecting ducts were also reactive in the fetal kidney to varying degrees. The distribution of TGF alpha reactivity in the mesonephros was similar to that observed for EGF but with a lower intensity. In contrast, there was no reactivity in the metanephros, at least during the embyronic periods examined. By the 11th week of gestation, an intense reactivity for TGF alpha polipeptide was shown in the fetal kidney at the level of the proximal tubules and Bowman's capsule; distal tubules as well as all urinary structures from the collecting ducts to the pelvis were less reactive. Finally, EGF/TGF alpha receptor reactivity was identified by the 6th week of development, being more intense in the mesonephros at the level of the mesonephric duct cells. In the metanephros, the ureteric bud-derived branches were reactive, whereas most of the blastemic tissue did not stain. By the 11th week, only the collecting ducts and the remaining urinary structures contained reaction products: Reactivity was distributed to the tissues originating from the ureteric bud branching. Taking into account recent advances in knowledge about the biology of growth factors, the hypothesis is proposed that the secretory components (vesicles, glomerulus, and tubules) of renal anlagen might release the growth factors while the cells of the urinary tract (i.e., collecting duct, pelvis, etc.) may be their targets.
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            Laminin and β1 Integrin Distribution in the Early Stages of Human Kidney Development

            Laminin, an extracellular matrix molecule (EMM) widely expressed in the basal laminae, interacts with specific membrane receptors among which the integrin molecules are the best known. During embryo development laminin is the first synthesized EMM and plays a significant role in the morphogenesis of organs in which epithelial-mesenchymal interactions and branching take place. The present study describes the distribution of laminin and of β1 integrin receptors during the very early stages of human kidney development. The observations were carried out on paraffin sections of human embryos ranging between the 4th and the 7th gestational week. Laminin was detected within the basement membranes of mesonephric duct, vesicles, glomerular vessels and celomic epithelium. The metanephric anlage reacted with anti-laminin immunoglobulins in the basement membrane underlying the ampullae and in few blastemic cap cells. Low levels of β1 integrin reactivity were found in both the mesonephric and metanephric structures. This study provides for the first time data about the distribution of laminin and β1 integrin in the early stages of human renal organogenesis suggesting a key role for these molecules in the epithelial-mesenchymal interactions necessary for kidney development.

              Author and article information

              Nephron Exp Nephrol
              Cardiorenal Medicine
              S. Karger AG
              April 2001
              11 January 2001
              : 9
              : 2
              : 90-98
              Section of Histology and General Embryology, Department of Human Morphology and Applied Biology, Faculty of Medicine and Surgery, Pisa University, Pisa, Italy
              52599 Exp Nephrol 2001;9:90–98
              © 2001 S. Karger AG, Basel

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              Figures: 4, Tables: 1, References: 25, Pages: 9
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