Development Of Tubular Structures Research Articles

Postnatal renal tubule development: roles of tubular flow and flux.

Postnatal renal tubule development is critical to adult kidney function. Several postnatal changes regulate the differentiation and proliferation of renal tubular cells. Here, we review the literature and our efforts on thick ascending limb (TAL) development in Bartter syndrome (BS). Glomerular filtrate quickly increases after birth, imposing fluid shear stress and circumferential stretch on immature renal tubules. Recent studies showed that kidney organoids under flow (superfusion) have better development of tubular structures and the expression of cilia and solute transporters. These effects are likely mediated by mechanosensors, such as cilia and the piezo1 channel. Improved renal oxygenation and sodium pump-dependent active transport can stimulate mitochondrial respiration and biogenesis. The functional coupling between transport and mitochondria ensures ATP supply for energy-demanding reactions in tubular cells, including cell cycle progression and proliferation. We recently discovered that postnatal renal medulla maturation and TAL elongation are impaired in Clc-k2-deficient BS mice. Primary cultured Clc-k2-deficient TAL cells have G1-S transition and proliferation delay. These developmental defects could be part of the early pathogenesis of BS and worsen the phenotype. Understanding how tubular flow and transepithelial ion fluxes regulate renal tubule development may improve the treatment of congenital renal tubulopathies.

Modifications in integrin expression and extracellular matrix composition in children with biliary atresia.

The aetiology of biliary atresia (BA) is still unresolved. The study's aim was to investigate the distribution of extracellular matrix proteins and cellular adhesion molecules in children with BA compared to other cholestatic liver disease (CLD) and normal liver architecture (NLA). Liver biopsies were obtained from children with BA (n=13), CLD (n=6) and NLA (n=8). We systematically analysed ultra thin frozen sections from the liver hilum stained with 25 monoclonal antibodies for cellular characterisation, extracellular matrix proteins and adhesion molecules. 2 changes were specifically found in BA: laminin beta1 was reduced in children with BA vs. NLA and CLD. Conversely, integrin alpha 3 was increased in BA vs. NLA and CLD (p<0.05). Furthermore, we detected changes in a similar pattern for both BA and CLD vs. NLA: in BA and CLD perlecan was increased. On the contrary, integrin beta1 and entactin were decreased vs. NLA (p<0.05). Extracellular matrix proteins and adhesion molecules mediate cellular polarity and integrity, development of tubular structures, and proliferation. Therefore, our findings can be important for the understanding of the genesis of BA. The composition of extracellular matrix proteins and adhesion molecules in children with BA differs from NLA and other CLD in distribution of laminin beta1 and integrin alpha 3, which may have implications for genetic, immunologic and environmental associations in BA.

Modulation of HGF-Induced Tubulogenesis and Branching by Multiple Phosphorylation Mechanisms

MDCK cells cultured in Type I collagen gels can be induced to develop branching tubular structures with demonstrable lumens in the presence of hepatocyte growth factor (HGF). As we have now shown by immunofluorescent localization of specific marker proteins, these tubules retain apical-basolateral polarity. However, the secondary signaling events which lead to these characteristic morphogenetic changes induced by HGF remain largely unelucidated. In order to examine these signaling events, particularly the role of protein phosphorylation in the formation of branching tubular structures, Madin-Darby canine kidney (MDCK) cells in collagen gels were treated with HGF plus well-characterized agents that affect protein phosphorylation. We quantified the formation of branching processes, an early step in the development of tubular structures in this model. Protein kinase C (PKC) inhibition resulted in more complex branching processes in the presence of HGF, when compared with HGF alone. In contrast, treatment with activators of protein kinase A (PKA), as well as calmod ulin antagonists, caused a marked decline in process formation. Consistent with an important role for protein phosphorylation in HGF-induced morphogenesis, protein phosphatase inhibition by okadaic acid or calyculin A was found to markedly inhibit process formation. Tyrosine kinase (TK) inhibition also decreased the percentage of processes. This is consistent with data indicating that one of the HGF receptors is identical to the c-met protooncogene product, which is known to possess TK activity. Our results suggest that the HGF-mediated induction of branching processes in MDCK cells, an early step in the development of branching tubular structures, can be modulated by multiple phosphorylation mechanisms including those mediated by PKC, PKA, and Ca2+/calmodulin-dependent kinase(s). We discuss how these phosphorylation events may play crucial roles in determining the degree of tubule formation and their length, as well as the extent of their arborization during the early development of epithelial tissues.

Electron microscope study of mouse liver infected by ectromelia virus

The livers of mice infected with the mouse pox virus were studied with the electron microscope. Several developmental forms and the mature form of the virus were found which correspond with those of other pox viruses. Alterations in hepatic parenchymal cell ultrastructure include a loss of glycogen, vesiculation of ergastoplasmic cisternae, swelling of the mitochondria and accumulations of lipid globules in the cytoplasm and within ergastoplasmic vesicles. These changes are not specific reactions to the disease. Other phenomena which do appear to be associated with the presence of the virus include the appearance of small foci of very dense granules in the nucleoli, the development of tubular structures around lipid globules that are entrapped within the viral matrix area, and the formation of cytoplasmic parallel lamellae associated with the mature virus particles. The parenchymal cells become necrotic before virus development in their cytoplasm is completed, but mature virus particles are found in the reticulo-endothelial cells lining the sinusoids.