A5081692861- Ion Transport and Channel Regulation
- Renal and related cancers
- Pancreatic function and diabetes
- Genetic and Kidney Cyst Diseases
- Dialysis and Renal Disease Management
- Pluripotent Stem Cells Research
- Renal Diseases and Glomerulopathies
- Potassium and Related Disorders
- Metabolism, Diabetes, and Cancer
- Chemotherapy-induced organ toxicity mitigation
- Aortic Disease and Treatment Approaches
- Genetic Syndromes and Imprinting
- Aortic aneurysm repair treatments
- Hormonal Regulation and Hypertension
- Cardiac, Anesthesia and Surgical Outcomes
- Chronic Kidney Disease and Diabetes
- Organ Donation and Transplantation
- Blood Coagulation and Thrombosis Mechanisms
- COVID-19 Clinical Research Studies
- Magnesium in Health and Disease
- Pediatric Urology and Nephrology Studies
- Diet, Metabolism, and Disease
- Electrolyte and hormonal disorders
- Cell Adhesion Molecules Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Tokyo Medical and Dental University
2015-2025
The University of Tokyo
2019-2024
Institute of Science Tokyo
2024
Brigham and Women's Hospital
2017-2023
Harvard University
2017-2023
RELX Group (United States)
2020
Fukuoka University
2013-2019
Health First
2018
Tri-Service General Hospital
2013
National Defense Medical Center
2013
Mutations in WNK kinases cause the human hypertensive disease pseudohypoaldosteronism type II (PHAII), but regulatory mechanisms of are not well understood. kelch-like 3 (KLHL3) and Cullin3 were also recently identified as causing PHAII. Therefore, new insights into hypertension can be gained by determining how these components interact they involved pathogenesis Here, we found that KLHL3 interacted with WNK4, induced WNK4 ubiquitination, reduced protein level. The interaction PHAII-causing...
Background Kidney injury is characterized by persisting inflammation and fibrosis, yet mechanisms which inflammatory signals drive fibrogenesis remain poorly defined. Methods RNA sequencing of fibrotic kidneys from patients with CKD identified a metabolic gene signature comprising loss mitochondrial oxidative phosphorylation expression concomitant increase in regulators enzymes glycolysis under the control PGC1 α MYC transcription factors, respectively. We modeled this switch vivo ,...
Kidneys have the capacity for intrinsic repair, preserving kidney architecture with return to a basal state after tubular injury. When injury is overwhelming or repetitive, however, that exceeded and incomplete repair results in fibrotic tissue replacing normal parenchyma. Loss of nephrons correlates reduced function, which defines chronic disease (CKD) confers substantial morbidity mortality worldwide population. Despite identification pathways involved limited treatments CKD exist, partly...
Chronic kidney disease (CKD) accelerates vascular calcification via phenotypic switching of smooth muscle cells (VSMCs). We investigated the roles circulating small extracellular vesicles (sEVs) between kidneys and VSMCs uncovered relevant sEV-propagated microRNAs (miRNAs) their biological signaling pathways.We established CKD models in rats mice by adenine-induced tubulointerstitial fibrosis. Cultures A10 embryonic rat showed increased transcription osterix (Sp7), osteocalcin (Bglap),...
Pseudohypoaldosteronism type II (PHAII) is a hereditary disease characterized by salt-sensitive hypertension, hyperkalemia and metabolic acidosis, genes encoding with-no-lysine kinase 1 (WNK1) WNK4 kinases are known to be responsible. Recently, Kelch-like 3 (KLHL3) Cullin3, components of KLHL3-Cullin3 E3 ligase, were newly identified as responsible for PHAII. We have reported that the substrate ligase-mediated ubiquitination. However, WNK1 Na–Cl cotransporter (NCC) also ligase other groups....
Abstract Tolvaptan, a vasopressin type 2 receptor antagonist initially developed to increase free-water diuresis, has been approved for the treatment of autosomal dominant polycystic kidney disease in multiple countries. Furthermore, tolvaptan shown improve renal functions rodent models chronic (CKD); however, underlying molecular mechanisms remain unknown. CKD is characterized by increased levels oxidative stress, and an antioxidant transcription factor—nuclear factor erythroid 2-related...
Drug nephrotoxicity is a common healthcare problem in hospitalized patients and major limitation during drug development. Multi-segmented kidney organoids derived from human pluripotent stem cells may complement traditional cell culture animal experiments for assessment. Here we evaluate the capability of to investigate toxicity vitro . Kidney express renal transporters, OAT1, OAT3, OCT2, while proximal tubular line shows absence OAT1 OAT3. Tenofovir aristolochic acid (AA) induce injury...
Aging | doi:10.18632/aging.205164. Hisazumi Matsuki, Shintaro Mandai, Hiroki Shiwaku, Takaaki Koide, Naohiro Takahashi, Tomoki Yanagi, Shunsuke Inaba, Saaya Ida, Tamami Fujiki, Yutaro Mori, Fumiaki Ando, Takayasu Koichiro Susa, Soichiro Iimori, Eisei Sohara, Hidehiko Shinichi Uchida
Na–K–Cl cotransporter isoform 1 (NKCC1) is involved in the regulation of vascular smooth muscle cell contraction. Recently, with-no-lysine kinase (WNK)–STE20/SPS1-related proline/alanine-rich (SPAK)–NKCC1 phosphorylation cascade cells was found to be important tone. In this study, we investigated whether WNK–SPAK–NKCC1 mouse aortic tissue regulated by dietary salt intake and mechanisms responsible. Phosphorylation SPAK NKCC1 significantly reduced aorta high-salt–fed mice increased...
Mutations in the with-no-lysine kinase 1 (WNK1), WNK4, kelch-like 3 (KLHL3), and cullin3 (CUL3) genes are known to cause hereditary disease pseudohypoaldosteronism type II (PHAII). It was recently demonstrated that this results from defective degradation of WNK1 WNK4 by KLHL3/CUL3 ubiquitin ligase complex. However, other physiological vivo roles KLHL3 remain unclear. Therefore, here we generated KLHL3−/− mice expressed β-galactosidase (β-Gal) under control endogenous promoter. Immunoblots...
Recently, the monoallelic loss-of-function IFT140 variant was identified as a causative gene for autosomal dominant polycystic kidney disease (ADPKD). In patients with kidneys who have positive family history, >90% pathogenic variants in
Organoids are miniature organs developed through technology. Kidney organoids that originate from human inducible pluripotent stem cells (iPSCs) were to recreate renal diseases. However, it is impossible simultaneously produce kidney iPSCs of multiple individuals and in a single medium. We herein report the development adult tubular organoids, namely, "tubuloids," primary epithelial Kidneys eight patients who underwent nephrectomy due malignancy sectioned, tubule cultured; four had normal...
Recently, nephronophthisis (NPH) has been considered a monogenic cause of end-stage renal disease (ESRD) in adults. However, adult-onset NPH is difficult to accurately diagnose and not reported cohort study. In this study, we assessed the genetic background clinicopathologic features adult NPH.We investigated 18 sporadic patients who were suspected as having by biopsy. We analyzed 69 genes that hereditary cystic kidney compared findings between with without pathogenic mutations NPH-causing...
Abstract Fibronectin (FN) glomerulopathy (FNG), a rare autosomal hereditary renal disease, is characterized by proteinuria resulting from the massive accumulation of FN in glomeruli. It typically affects individuals aged 10–50 years. In this report, we describe case 57-year-old man who was diagnosed with FNG through genetic analysis and histological examination that revealed membranoproliferative glomerulonephritis. Despite treatment prednisolone, therapeutic response unsatisfactory....
Protein kinase A (PKA) directly phosphorylates aquaporin-2 (AQP2) water channels in renal collecting ducts to reabsorb from urine for the maintenance of systemic homeostasis. More than 50 functionally distinct PKA-anchoring proteins (AKAPs) respectively create compartmentalized PKA signaling determine substrate specificity PKA. Identification an AKAP responsible AQP2 phosphorylation is essential step toward elucidating molecular mechanisms urinary concentration. activation by several...