Publications by authors named "Takuto Seki"

Roxadustat is one of the oral hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) that stimulates erythropoiesis and regulates the genes related to iron metabolism. The treatment of HIF-PHIs is useful compared with that of erythropoietin stimulating agent (ESA) using various instruments and procedures. Few clinical researchers have examined the efficacy and safety of switching treatment from Darbepoetin to Roxadustat in Japanese hemodialysis (HD) patients.

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We report herein an adult case of chronic kidney disease (CKD) associated with diabetes. The patient had been treated with insulin injection for diabetes 10 years ago. At the time of his first visit to our division for further examinations, we diagnosed him as CKD: cause (C) diabetes; glomerular filtration rate (GFR) (G) G5 (estimated [e] GFR, 10.

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Article Synopsis
  • Rac1 is a protein that plays a significant role in various biological processes and its expression increases during podocyte injury, although its exact function in repair is uncertain.
  • Experiments with podocyte-specific Rac1 knockout mice showed increased detachment of podocytes and stronger adhesion of the glomerular basement membrane to Bowman's capsule compared to control mice, indicating that Rac1 is crucial for podocyte integrity during damage.
  • The findings suggest that Rac1 activates the mTOR pathway in podocytes, and its absence leads to reduced cell volume and stronger suppression of mTOR activity, which may contribute to the progression of kidney damage and glomerulosclerosis.
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The highly conserved spalt (sal) gene family members encode proteins characterized by multiple double zinc finger motifs of the C2H2 type. Humans and mice each have four known Sal-like genes (SALL1-4 in humans and Sall1-4 in mice). Sall1 is known to have a crucial role in kidney development.

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Membrane-associated guanylate kinase inverted 2 (MAGI-2) is a component of the slit diaphragm (SD) of glomerular podocytes. Here, we investigated the podocyte-specific function of MAGI-2 using newly generated podocyte-specific MAGI-2-knockout (MAGI-2-KO) mice. Compared with podocytes from wild-type mice, podocytes from MAGI-2-KO mice exhibited SD disruption, morphologic abnormalities of foot processes, and podocyte apoptosis leading to podocyte loss.

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The irreversibility of glomerulosclerotic changes depends on the degree of podocyte injury. We have previously demonstrated the endocytic translocation of podocin to the subcellular area in severely injured podocytes and found that this process is the primary disease trigger. Here we identified the protein sorting nexin 9 (SNX9) as a novel facilitator of podocin endocytosis in a yeast two-hybrid analysis.

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Studies have revealed many analogies between podocytes and neurons, and these analogies may be key to elucidating the pathogenesis of podocyte injury. Cathepsin D (CD) is a representative aspartic proteinase in lysosomes. Central nervous system neurons in CD-deficient mice exhibit a form of lysosomal storage disease with a phenotype resembling neuronal ceroid lipofuscinoses.

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Background And Objectives: Megalin is highly expressed at the apical membranes of proximal tubular epithelial cells. A urinary full-length megalin (C-megalin) assay is linked to the severity of diabetic nephropathy in type 2 diabetes. This study examined the relationship between levels of urinary C-megalin and histological findings in adult patients with IgA nephropathy (IgAN).

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Activation of Notch1 and Notch2 has been recently implicated in human glomerular diseases. Here we show that Notch2 prevents podocyte loss and nephrosis. Administration of a Notch2 agonistic monoclonal antibody ameliorates proteinuria and glomerulosclerosis in a mouse model of nephrosis and focal segmental glomerulosclerosis.

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Background: It has been reported that podocytopenia has been occurring with increasing disease severity in patients with IgA nephropathy (IgAN). Dendrin is localized at the slit diaphragm (SD) in podocytes. We showed that dendrin translocates to the nucleus of injured podocytes in experimental nephritis and the nuclear dendrin promotes podocyte apoptosis.

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Background And Objectives: Podocalyxin (PCX) is present on the apical cell membrane of podocytes and is shed in urine from injured podocytes. Urinary podocalyxin (u-PCX) is associated with severity of active glomerular injury in patients with glomerular diseases. This study examined the relationship between number of urinary podocytes, levels of u-PCX, and glomerular injury in adults with IgA nephropathy (IgAN).

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