ArticleJournal of the American Society of Nephrology : JASN2016
Cathepsin D in Podocytes Is Important in the Pathogenesis of Proteinuria and CKD.
Article in Journal of the American Society of Nephrology : JASN, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Urinary Proteomics Identifies Cathepsin D as a Biomarker of Rapid eGFR Decline in Type 1 Diabetes.Diabetes care · 2022Pooled it
- Lysosomal dysfunction in diabetes and diabetic complications.Frontiers in endocrinology · 2026Review
- A Novel Role of Neutrophil Elastase in Podocyte Dysfunction Induced by High Glucose, PMA, and MDP.Journal of cellular physiology · 2025Article
- Mechanisms and Therapeutic Perspectives of Podocyte Aging in Podocytopathies.International journal of molecular sciences · 2025Review
- Bioinformatic Insights and XGBoost Identify Shared Genetics in Chronic Obstructive Pulmonary Disease and Type 2 Diabetes.The clinical respiratory journal · 2025Article
- METTL10 attenuates adriamycin-induced podocyte injury by targeting cell dedifferentiation.Scientific reports · 2025Article
- Proteomic Changes Induced by the Immunosuppressant Everolimus in Human Podocytes.International journal of molecular sciences · 2024Article
- SGLT2 inhibition to target kidney aging.Clinical kidney journal · 2024Review
- Cytoskeleton Rearrangement in Podocytopathies: An Update.International journal of molecular sciences · 2024Review
- Asparagine endopeptidase protects podocytes in adriamycin-induced nephropathy by regulating actin dynamics through cleaving transgelin.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Omega-3 Fatty Acids Attenuate Renal Fibrosis via AMPK-Mediated Autophagy Flux Activation.Biomedicines · 2023Article
- Autophagy and mitophagy: physiological implications in kidney inflammation and diseases.American journal of physiology. Renal physiology · 2023Review
- Protective effect of the tunneling nanotube-TNFAIP2/M-sec system on podocyte autophagy in diabetic nephropathy.Autophagy · 2023Article
- Knockout of the neonatal Fc receptor alters immune complex trafficking and lysosomal function in cultured podocytes.PloS one · 2023Article
- Impaired autophagic flux and dedifferentiation in podocytes lacking Asah1 gene: Role of lysosomal TRPML1 channel.Biochimica et biophysica acta. Molecular cell research · 2023Article
- Hormonal Regulation of Renal Fibrosis.Life (Basel, Switzerland) · 2022Review
- Novel Markers in Diabetic Kidney Disease-Current State and Perspectives.Diagnostics (Basel, Switzerland) · 2022Review
- Human pluripotent stem cell-derived kidney organoids for personalized congenital and idiopathic nephrotic syndrome modeling.Development (Cambridge, England) · 2022Article
- Investigation of the Relationship between Cardiovascular Biomarkers and Brachial-Ankle Pulse Wave Velocity in Hemodialysis Patients.Journal of personalized medicine · 2022Article
- Mechanisms of podocyte injury and implications for diabetic nephropathy.Clinical science (London, England : 1979) · 2022Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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. In the kidney, the role of CD in podocytes has not been fully explored. Herein, we generated podocyte-specific CD-knockout mice that developed proteinuria at 5 months of age and ESRD by 20-22 months of age. Immunohistochemical analysis of these mice showed apoptotic podocyte death followed by proteinuria and glomerulosclerosis with aging. Using electron microscopy, we identified, in podocytes, granular osmiophilic deposits (GRODs), autophagosome/autolysosome-like bodies, and fingerprint profiles, typical hallmarks of CD-deficient neurons. CD deficiency in podocytes also led to the cessation of autolysosomal degradation and accumulation of proteins indicative of autophagy impairment and the mitochondrial ATP synthase subunit c accumulation in the GRODs, again similar to changes reported in CD-deficient neurons. Furthermore, both podocin and nephrin, two essential components of the slit diaphragm, translocated to Rab7- and lysosome-associated membrane glycoprotein 1-positive amphisomes/autolysosomes that accumulated in podocyte cell bodies in podocyte-specific CD-knockout mice. We hypothesize that defective lysosomal activity resulting in foot process effacement caused this accumulation of podocin and nephrin. Overall, our results suggest that loss of CD in podocytes causes autophagy impairment, triggering the accumulation of toxic subunit c-positive lipofuscins as well as slit diaphragm proteins followed by apoptotic cell death.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.