A5020010316- Renal Diseases and Glomerulopathies
- Autophagy in Disease and Therapy
- Genetic and Kidney Cyst Diseases
- Chronic Kidney Disease and Diabetes
- Lysosomal Storage Disorders Research
- Renal and related cancers
- Biomedical Research and Pathophysiology
- Tuberous Sclerosis Complex Research
- Celiac Disease Research and Management
- Neuroinflammation and Neurodegeneration Mechanisms
- Advanced Electron Microscopy Techniques and Applications
- Photosynthetic Processes and Mechanisms
- Advanced Fluorescence Microscopy Techniques
- Muscle Physiology and Disorders
- Genetic Syndromes and Imprinting
- Acute Kidney Injury Research
- Neuroscience and Neuropharmacology Research
- Lymphatic Disorders and Treatments
- Cellular transport and secretion
- Hair Growth and Disorders
- Optical Coherence Tomography Applications
- Blood properties and coagulation
- Neurological disorders and treatments
- Wound Healing and Treatments
- Developmental Biology and Gene Regulation
Juntendo University
2012-2024
Kyoto University
2015-2023
Kagoshima University
2021
Teikyo University
2016
Bunkyo University
2014
Studies have revealed many analogies between podocytes and neurons, these may be key to elucidating the pathogenesis of podocyte injury. Cathepsin D (CD) is a representative aspartic proteinase in lysosomes. Central nervous system neurons CD-deficient mice exhibit form lysosomal storage disease with phenotype resembling neuronal ceroid lipofuscinoses. In kidney, role CD has not been fully explored. Herein, we generated podocyte–specific CD–knockout that developed proteinuria at 5 months age...
Skeletal muscle atrophy is thought to result from hyperactivation of intracellular protein degradation pathways, including autophagy and the ubiquitin–proteasome system. However, precise contributions these pathways are unclear. Here, we show that an deficiency in denervated slow-twitch soleus muscles delayed skeletal atrophy, reduced mitochondrial activity, induced oxidative stress accumulation PARK2/Parkin, which participates quality control (PARK2-mediated mitophagy), mitochondria. Soleus...
The renal glomerulus produces primary urine from blood plasma by ultrafiltration. ultrastructure of the is closely related to filtration function and disease development. glomeruli has mainly been evaluated using transmission electron microscopy; however, volume that can be observed microscopy extremely limited relative total glomerulus. Consequently, observing structures exist in only one location each glomerulus, such as vascular pole, evaluating low-density or localized lesions are...
Membrane-associated guanylate kinase inverted 2 (MAGI-2) is a component of the slit diaphragm (SD) glomerular podocytes. Here, we investigated podocyte-specific function MAGI-2 using newly generated MAGI-2–knockout (MAGI-2–KO) mice. Compared with podocytes from wild-type mice, MAGI-2–KO mice exhibited SD disruption, morphologic abnormalities foot processes, and podocyte apoptosis leading to loss. These pathologic changes manifested as massive albuminuria by 8 weeks age glomerulosclerosis...
Post-fixation with osmium tetroxide staining and the embedding of Epon are robust essential treatments that used to preserve visualize intracellular membranous structures during electron microscopic analyses. These treatments, however, can significantly diminish fluorescent intensity most proteins in cells, which creates an obstacle for in-resin correlative light-electron microscopy (CLEM) Epon-embedded cells. In this study, we a far-red protein retains fluorescence after perform CLEM...
Abstract Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive accumulation of hepatic triglycerides (TG) and hyperglycemia arising due to persistent insulin resistance, profoundly linked obesity. However, there currently no established treatment for NAFLD in obese human subjects. We previously isolated Helz2, the expression which was upregulated mouse NAFLD, its deletion activated functional leptin receptor long form (Leprb) suppressed development body weight (BW) gain...
Background and Objectives Megalin is highly expressed at the apical membranes of proximal tubular epithelial cells. A urinary full-length megalin (C-megalin) assay linked to severity diabetic nephropathy in type 2 diabetes. This study examined relationship between levels C-megalin histological findings adult patients with IgA (IgAN). Design, Setting, Participants, & Measurements Urine samples voided morning on day renal biopsy were obtained from 73 IgAN (29 men 44 women; mean age, 33 years)...
Renal proximal tubular epithelial cells are significantly damaged during acute kidney injury. cell-specific autophagy-deficient mice show increased sensitivity against renal injury, while showing few pathological defects under normal fed conditions. Considering that autophagy protects the from it is reasonable to assume contributes maintenance of To clarify this possibility, we generated a knock out mouse model which lacks Atg7, key autophagosome forming enzyme, in (Atg7flox/flox;KAP-Cre+)....
Cathepsin D is one of the major lysosomal aspartic proteases that essential for normal functioning autophagy-lysosomal system. In kidney, cathepsin enriched in renal proximal tubular epithelial cells, and its levels increase during acute kidney injury. To investigate how D-deficiency impacts we employed a conditional knockout CtsDflox/−; Spink3Cre mouse. Immunohistochemical analyses using anti-cathepsin antibody revealed was significantly decreased cells cortico-medullary region, mainly this...
Abstract In-resin CLEM of Epon embedded samples can greatly simplify the correlation fluorescent images with electron micrographs. The usefulness this technique is limited at present by low number proteins that resist processing. Additionally, no study has reported possibility two-color in-resin cells. In study, we screened for monomeric green and red We identified mWasabi, CoGFP variant 0, mCherry2; two one as alternatives CLEM. expressed mitochondria-localized mCherry2 histone H2B tagged 0...
We generated a new transgenic mouse model that expresses pHluorin-mKate2 fluorescent protein fused with human LC3B (PK-LC3 mice) for monitoring autophagy activity in neurons of the central nervous system. Histological analysis revealed puncta cerebral cortex, hippocampus, cerebellar Purkinje cells, and anterior spinal regions. Using CLEM analysis, we confirmed PK-LC3-positive perikarya cells correspond to autophagic structures. To validate usability PK-LC3 mice, quantified mice kept normal...
Podocytes are highly specialized cells within the glomerulus that essential for ultrafiltration. The slit diaphragm between foot processes of podocytes functions as a final filtration barrier to prevent serum protein leakage into urine. slit-diaphragm consists mainly Nephrin and Neph1, localization these backbone proteins is maintaining integrity glomerular barrier. However, mechanisms regulate have remained elusive. Here, we focused on role membrane-associated guanylate kinase inverted 2...
Ferulic acid (FA), a naturally occurring polyphenol abundant in vegetables and rice bran, is known to possess potent antioxidant activity, thereby protecting cells from oxidative stress. In the present study, we show that addition its anti-oxidant ferulic exerts substantial inhibitory activity on cellular mammalian target of rapamycin (mTor)-signaling pathways. HeLa mouse primary hepatocytes cultured with conventional nutrient-rich media, (1 mM) elicited dephosphorylation S6 kinase substrate...
Podocytes serve as the final barrier to urinary protein loss through a highly specialized structure called slit membrane and maintain foot process glomerular basement membranes. Podocyte injury results in progressive damage accelerates sclerotic changes, although exact mechanism of podocyte is still obscure. We focus on staining gap (podocin gap) defined difference between podocin synaptopodin, which are normally located process. In puromycin aminonucleoside nephrosis rats, significantly...
Significance Statement The ubiquitin-proteasome system (UPS) and the autophagy-lysosomal (APLS) are major intracellular protein degradation mechanisms. importance of APLS in podocytes is established, but role UPS not well understood. first mouse model podocyte-specific proteasome impairment revealed that plays important roles podocyte homeostasis, inducing p53-mediated apoptosis mTOR-mediated autophagy suppression. with impaired proteasomes exhibited characteristic features aging increase a...
Abstract Neuronal ceroid lipofuscinosis is one of many neurodegenerative storage diseases characterized by excessive accumulation lipofuscins. CLN10 disease, an early infantile neuronal lipofuscinosis, associated with a gene that encodes cathepsin D (CtsD), the major lysosomal proteases. Whole body CtsD-knockout mice show phenotypes lipofuscins in brain and also defects other tissues including intestinal necrosis. To clarify precise role CtsD central nervous system (CNS), we generated...
Autophagy is a process of cellular degradation, and its dysfunction elicits many pathological symptoms. However, the contribution autophagy to kidney glomerular function has not been fully clarified. We previously reported that LC3, promising executor autophagy, played an important role in recovery from podocyte damage experimental nephrosis model (Asanuma K, Tanida I, Shirato Ueno T, Takahara H, Nishitani Kominami E, Tomino Y. FASEB J 17: 1165-1167, 2003). γ-Aminobutyric acid A...
Abstract Rac1, a Rho family member, is ubiquitously expressed and participates in various biological processes. Rac1 expression induced early podocyte injury, but its role repair unclear. To investigate the of podocytes under pathological conditions, we used podocyte-specific conditional knock-out (cKO) mice administered adriamycin (ADR), which causes nephrosis glomerulosclerosis. Larger areas detached podocytes, more adhesion GBM to Bowman’s capsule, higher ratio sclerotic glomeruli were...