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- Professor, Faculty of Health Science, Juntendo University順天堂大学保険医療学部教授Research activities in the functional anatomy o... moreProfessor, Faculty of Health Science, Juntendo University順天堂大学保険医療学部教授Research activities in the functional anatomy of skeletal muscles, and in the history of medicine.研究活動：骨格筋の機能解剖学、医史学edit
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Podocytes present a unique 3D architecture specialized for glomerular filtration. However, several 3D morphological aspects on podocyte development remain partially understood because they are difficult to reveal using conventional... more
Podocytes present a unique 3D architecture specialized for glomerular filtration. However, several 3D morphological aspects on podocyte development remain partially understood because they are difficult to reveal using conventional scanning electron microscopy (SEM). Here, we adopted serial block-face SEM imaging, a powerful tool for analyzing the three-dimensional cellular ultrastructure, to precisely reveal the morphological process of podocyte development, such as the formation of foot processes (FPs). Development of FPs presents three morphological states: the primitive, immature, and mature FPs. Immature podocytes were columnar in shape and connected to each other by the junctional complex (JC), which migrated toward the basal side of the cell. When the JC was close to the basement membrane, immature podocytes started to interdigitate with primitive FPs under the level of JC. As primitive FPs lengthened, the JC moved between primitive FPs to form immature FPs. Finally, the JC w...
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Block-face imaging is a scanning electron microscopic technique which enables easier acquisition of serial ultrastructural images directly from the surface of resin-embedded biological samples with a similar quality to transmission... more
Block-face imaging is a scanning electron microscopic technique which enables easier acquisition of serial ultrastructural images directly from the surface of resin-embedded biological samples with a similar quality to transmission electron micrographs. In the present study, we analyzed the three-dimensional architecture of podocytes using serial block-face imaging. It was previously believed that podocytes are divided into three kinds of subcellular compartment: cell body, primary process, and foot process, which are simply aligned in this order. When the reconstructed podocytes were viewed from their basal side, the foot processes were branched from a ridge-like prominence, which was formed on the basal surface of the primary process and was similar to the usual foot processes in structure. Moreover, from the cell body, the foot processes were also emerged via the ridge-like prominence, as found in the primary process. The ridge-like prominence anchored the cell body and primary p...
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Research Interests: Biology, Medicine, Extracellular Matrix, Anatomy, Capillaries, and 15 moreBasement Membrane, Animals, Male, Ultrastructure, Diabetic Nephropathy, Clinical Sciences, Rats, Granular Material, Surface Area, Streptozotocin, Experimental Diabetes Mellitus Type 1 and 2, Diabetic Rat, Glomerulus, Renal Glomerulus, and Kidney glomerulus
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Research Interests: Electron Microscopy, Biology, Acute kidney injury, Scanning Electron Microscopy, Transmission Electron Microscopy, and 15 moreMedicine, Kidney, Capillaries, Basement Membrane, Animals, Complex network, Male, Perfusion, Clinical Sciences, Rats, Glomerulus, Renal Glomerulus, Hydrostatic Pressure, In Vitro Techniques, and Kidney glomerulus
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Research Interests: Endocrinology, Biology, Scanning Electron Microscopy, Medicine, Extracellular Matrix, and 14 moreSignal Transduction, Population, Internal Medicine, Kidney, Mice, Renin Angiotensin Aldosterone System, Animals, Hyperplasia, Phenotype, Clinical Sciences, Receptor, Renal Artery, Angiotensin II, and Vascular Smooth Muscle
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Research Interests: Molecular Biology, Fluorescence Microscopy, Biology, Membrane Proteins, Immunohistochemistry, and 15 moreMedicine, In Situ Hybridization, Kidney, Animals, Podocyte cell biology, Clinical Sciences, Amino Acid Profile, Molecular weight, Monoclonal Antibody, Podocyte, Immunostaining, Molecular Structure, Cadherins, Adherens Junction, and Kidney glomerulus
ABSTRACT. Podocin is identified as a product of the gene mutated in a patient with autosomal recessive steroid-resistant nephrotic syndrome. Although podocin is reported to be located at the slit diaphragm area, the precise role of... more
ABSTRACT. Podocin is identified as a product of the gene mutated in a patient with autosomal recessive steroid-resistant nephrotic syndrome. Although podocin is reported to be located at the slit diaphragm area, the precise role of podocin for maintaining the barrier function of the slit diaphragm has not been clearly elucidated. A rat homologue of podocin was cloned, and the expression of podocin was investigated and then compared with the nephrin and the ZO-1 expressions in rat experimental proteinuric models and in developing glomeruli. Amino acid sequences of rat and human podocin are highly homologous (84.3% identity). The domain structure of podocin is also highly conserved between rat and human. The mRNA expression for podocin was detected in glomeruli and the nerve tissues. The localization of podocin has close proximity to that of nephrin in normal adult rat glomeruli. Podocin staining was restricted to the basal side of the podocyte of the early developing stage, whereas n...
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In rat lung, the definitive alveoli are established during development by the outgrowth of secondary septa from the primary septa present in newborn; however, the mechanism of alveolar formation has not yet been fully clarified. In this... more
In rat lung, the definitive alveoli are established during development by the outgrowth of secondary septa from the primary septa present in newborn; however, the mechanism of alveolar formation has not yet been fully clarified. In this study, we characterize the septal interstitial cells in developing alveoli. During the perinatal period, alpha-SMA–containing slender cells were found in the primitive alveolar septa. Alpha-SMA–containing cells were detected at the tips of the septa until postnatal day 21, when the alveolar formation was almost completed, but disappeared in adult. Immunoelectron microscopy demonstrated that alpha-SMA is localized mainly in the cellular protrusions, which are connected with the elastic fibers around the interstitial cells. Developmentally regulated brain protein (drebrin) is also located in the cell extensions containing alpha-SMA in immature alveolar interstitial cells. In adult lung, alpha-SMA–positive cells are located only at the alveolar ducts bu...
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The function of actin cytoskeleton in mesangial cells (MCs) during the recovering process of injured glomeruli is not fully understood. MCs in injured glomeruli express α-smooth muscle actin (α-SMA), which is not detected in normal... more
The function of actin cytoskeleton in mesangial cells (MCs) during the recovering process of injured glomeruli is not fully understood. MCs in injured glomeruli express α-smooth muscle actin (α-SMA), which is not detected in normal glomeruli. We focused on the localization of α-SMA in MCs of Thy-1. 1 nephritic rat. Expression of α-SMA in the injured glomeruli peaked at day 5 after antibody injection and then declined gradually. At day 5, MCs, where α-SMA was localized at their cytoplasmic processes situated in various positions, occupied the expanded mesangium. MCs expressing α-SMA tended to be located at the peripheral region close to the glomerular basement membrane (GBM) or endothelial cells at day 8. Localization of α-SMA within the peripheral MCs was restricted to the cytoplasmic processes radiating toward the GBM and touching it with their tips at day 8. These α-SMA-containing processes are suitable to transmit the contractile force to GBM and may contribute to normalize the e...
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The branching and distribution patterns of the superior mesenteric artery were studied in 10 adult bullfrogs (Rana catesbeiana) after injection of coloured latex solution into the vasculature. The abdominal digestive organs in the... more
The branching and distribution patterns of the superior mesenteric artery were studied in 10 adult bullfrogs (Rana catesbeiana) after injection of coloured latex solution into the vasculature. The abdominal digestive organs in the bullfrog were mainly supplied by the coeliac artery and the superior mesenteric artery, both of which arose as a common trunk, the coeliacomesenteric artery, from the abdominal aorta. The coeliac artery supplied the stomach, liver, gallbladder and the pancreas, whereas the first branch of the superior mesenteric artery was the splenic artery with other branches supplying the greater part of intestine. The apex of the intestinal loop was defined as the region supplied by the trunk of the superior mesenteric artery, and its intestinal branches constituted a ‘nested formation' which had the following characteristics. (1) The branches of the trunk were distributed to both sides of the apex, and the distribution regions of younger branches were located more...
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Four forelimbs of 3 platypuses and 3 forelimbs of 2 echidnas were examined to study the precise form of the brachial plexus and to clarify the structural characteristics of the brachial plexus in phylogeny. The spinal components... more
Four forelimbs of 3 platypuses and 3 forelimbs of 2 echidnas were examined to study the precise form of the brachial plexus and to clarify the structural characteristics of the brachial plexus in phylogeny. The spinal components contributing to the plexus (C4–T2) and the formation patterns of the 3 trunks of the plexus were the same as those generally observed in mammals. In the cranial half of the brachial plexus from C4, 5 and 6 in monotremes, division into the ventral bundle (lateral cord) and dorsal bundle (axillary nerve) is clear, as in other mammals. However, for monotremes, in the caudal half of the plexus from C7 and T1 (+T2) and the nerves arising from the caudal plexus there is no definite division into the ventral and dorsal bundles, which distribute to the flexor and extensor parts of the forelimbs, respectively. The lower trunk of the monotreme brachial plexus forms a cord which contains both ventral and dorsal components. This characteristic diverges from the generall...
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Background: The podocyte slit diaphragm (SD) is an essential component of the selective filtration barrier in the glomerulus. Several structural proteins required for formation and maintenance of SD have been identified; however,... more
Background: The podocyte slit diaphragm (SD) is an essential component of the selective filtration barrier in the glomerulus. Several structural proteins required for formation and maintenance of SD have been identified; however, molecular mechanisms regulating these proteins are still limited. Results: Here, we demonstrate that MAGUK p55 subfamily member 5a (Mpp5a)/Nagie oko, a component of the Crb multi‐protein complex, was colocalized with an SD‐associated protein ZO‐1 in the zebrafish pronephric glomerulus. To characterize the function of Mpp5a, zebrafish mpp5am520 mutant embryos, which are known to have defects in cardiac and neuronal morphogenesis, were analyzed. These mutants failed to merge the bilateral glomerular primordia and to form the glomerular capillary and mesangium, but the foot processes and SD showed normal appearance. The structural disorganization in the mpp5am520 mutant glomerulus was quite similar to that of a cardiac troponin T2a/tnnt2a/silent heart knockdow...
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We investigated the actin filament organization and immunolocalization of actin-binding proteins (alpha-actinin and cortactin) in the podocyte foot processes of eight vertebrate species (lamprey, carp, newt, frog, gecko, turtle, quail,... more
We investigated the actin filament organization and immunolocalization of actin-binding proteins (alpha-actinin and cortactin) in the podocyte foot processes of eight vertebrate species (lamprey, carp, newt, frog, gecko, turtle, quail, and rat). Three types of actin cytoskeleton were found in these foot processes. (1) A cortical actin network with cortactin filling the space between the plasma membrane and the other actin cytoskeletons described below was found in all of the species examined here. The data indicated that the cortical actin network was the minimal essential actin cytoskeleton for the formation and maintenance of the foot processes in vertebrate podocytes. (2) An actin bundle with alpha-actinin existing along the longitudinal axis of foot process above the level of slit diaphragms was only observed in quail and rat. (3) An actin fascicle consisting of much fewer numbers of actin filaments than that of the actin bundle was observed in the species other than quail and rat, but at various frequencies. These findings suggest that the actin bundle is an additional actin cytoskeleton reflecting a functional state peculiar to quail and rat glomeruli. Considering the higher intraglomerular pressure and the extremely thin filtration barrier in birds and mammals, the foot processes probably mainly protect the thinner filtration barrier from the higher internal pressure occurring in quail and rat glomeruli. Therefore, we consider that the actin bundle plays a crucial role in the mechanical protection of the filtration barrier. Moreover, the actin fascicle may be a potential precursor of the actin bundle.
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The renal glomerulus consists of endothelial cells, podocytes, and mesangial cells. These cells cooperate with each other for glomerular filtration; however, the intercellular signaling molecules between glomerular cells are not fully... more
The renal glomerulus consists of endothelial cells, podocytes, and mesangial cells. These cells cooperate with each other for glomerular filtration; however, the intercellular signaling molecules between glomerular cells are not fully determined. Tyrosine phosphorylation of slit diaphragm molecules is a key to the detection of the signal to podocytes from other cells. Although src kinase is involved in this event, the molecules working for dephosphorylation remain unclear. We demonstrate that signal-inhibitory regulatory protein (SIRP)-α, which recruits a broadly distributed tyrosine dephosphorylase SHP-2 to the plasma membrane, is located in podocytes. SIRP-α is a type I transmembrane glycoprotein, which has three immunoglobulin-like domains in the extracellular region and two SH2 binding motifs in the cytoplasm. This molecule functions as a scaffold for many proteins, especially the SHP-2 molecule. SIRP-α is concentrated in the slit diaphragm region of normal podocytes. CD47, a li...
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The ultrastructure and size distributions of collagen fibrils in Glisson's sheath were investigated in the rat liver to analyse the mechanical environment around the fibrils and their possible cells of origin. Glisson's... more
The ultrastructure and size distributions of collagen fibrils in Glisson's sheath were investigated in the rat liver to analyse the mechanical environment around the fibrils and their possible cells of origin. Glisson's sheath was found to contain 2 populations of collagen fibrils with different diameters and distinct localisations, namely fibroblast-associated and bile epithelium-associated. Fibroblast-associated collagen was composed of fibrils arranged in bundles and constituted the majority of the collagen in Glisson's sheath. Bile epithelium-associated collagen was represented by small dispersed groups of fibrils just beneath the basement membrane of the bile duct. The basement membrane of the bile duct was frequently reduplicated into a few or as many as 10 layers of laminae densae, with scattered collagen fibrils between these laminae. The diameters of the fibrils of both groups of collagen increased in relation to the calibre of the bile duct, whereas at any given place in Glisson's sheath bile epithelium-associated collagen fibrils had a smaller diameter compared with those of the fibroblast-associated fibrils. The increment in fibril diameter along the bile duct is considered to be correlated with the increase in mechanical stress acting on Glisson's sheath. The difference in diameter between the 2 populations as well as the incorporation of fibrils between the laminae densae of the basement membrane of the bile duct supports the view that the bile epithelium-associated collagen is produced by the epithelial cells of the bile duct, thus having a different origin from that of fibroblast-associated collagen. These findings provide the first evidence that the epithelial cells of the interlobular bile duct produce fibril-forming collagen. Furthermore, it is suggested that cholestasis stimulates the epithelial cells of interlobular bile duct to increased synthesis of fibril-forming collagen that is also produced by these cells under physiological conditions.