ArticleProceedings of the National Academy of Sciences of the United States of America2019
Discovery of endoplasmic reticulum calcium stabilizers to rescue ER-stressed podocytes in nephrotic syndrome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 61 citations in OpenAlex.
- MANF clears mutant uromodulin in human kidney organoids of autosomal dominant tubulointerstitial kidney disease.The Journal of clinical investigation · 2026Article
- GADD45A may be a potential biomarker associated with endoplasmic reticulum stress in focal segmental glomerulosclerosis.Biochemistry and biophysics reports · 2026Article
- MANF safeguards mitochondria-associated endoplasmic reticulum membrane integrity in nucleus pulposus-derived mesenchymal stem cells to maintain homeostasis of the intervertebral disc.Cell biology and toxicology · 2026Article
- Reactive oxygen species-evoked endoplasmic reticulum stress mediates albumin load-induced epithelial-mesenchymal transition in podocytes.Molecular biology reports · 2026Article
- Talin1 modulates the Piezo1-YAP axis to regulate endothelial cell inflammation and atherosclerosis.Cellular and molecular life sciences : CMLS · 2025Article
- Research Trends and Hotspots in Hypertrophic Scar: A Bibliometric Analysis over the Past Five Decades.Aesthetic plastic surgery · 2025Article
- Molecular mechanisms attributed to colistin renal proximal tubular epithelial cytotoxicity.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2025Review
- Lysosome stress response and mitochondria injury are the earliest detectable alteration in FSGS.Scientific reports · 2025Article
- Identification and validation of the pivotal role of MANF gene in pancreatic β-cell aging using bioinformatics.Biochemistry and biophysics reports · 2025Article
- The intelligent podocyte: sensing and responding to a complex microenvironment.Nature reviews. Nephrology · 2025Review
- Targeting endoplasmic reticulum stress: an innovative therapeutic strategy for podocyte-related kidney diseases.Journal of translational medicine · 2025Review
- Heterogeneous enhancer states orchestrate β cell responses to metabolic stress.Nature communications · 2024Article
- Oxysterol-binding protein-like 7 deficiency leads to ER stress-mediated apoptosis in podocytes and proteinuria.American journal of physiology. Renal physiology · 2024Article
- Calcium signalling and transport in the kidney.Nature reviews. Nephrology · 2024Review
- ER Stress-Perturbed Intracellular Protein O-GlcNAcylation Aggravates Podocyte Injury in Diabetes Nephropathy.International journal of molecular sciences · 2023Article
- MANF stimulates autophagy and restores mitochondrial homeostasis to treat autosomal dominant tubulointerstitial kidney disease in mice.Nature communications · 2023Article
- Podocyte-specific deletion of ubiquitin carboxyl-terminal hydrolase L1 causes podocyte injury by inducing endoplasmic reticulum stress.Cellular and molecular life sciences : CMLS · 2023Article
- Analysis of gene expression and use of connectivity mapping to identify drugs for treatment of human glomerulopathies.Frontiers in medicine · 2023Article
- An ex vivo culture model of kidney podocyte injury reveals mechanosensitive, synaptopodin-templating, sarcomere-like structures.Science advances · 2022Article
- Blocking CHOP-dependent TXNIP shuttling to mitochondria attenuates albuminuria and mitigates kidney injury in nephrotic syndrome.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
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8 authors at 3 institutions in 2 countries.
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Abstract
Emerging evidence has established primary nephrotic syndrome (NS), including focal segmental glomerulosclerosis (FSGS), as a primary podocytopathy. Despite the underlying importance of podocyte endoplasmic reticulum (ER) stress in the pathogenesis of NS, no treatment currently targets the podocyte ER. In our monogenic podocyte ER stress-induced NS/FSGS mouse model, the podocyte type 2 ryanodine receptor (RyR2)/calcium release channel on the ER was phosphorylated, resulting in ER calcium leak and cytosolic calcium elevation. The altered intracellular calcium homeostasis led to activation of calcium-dependent cytosolic protease calpain 2 and cleavage of its important downstream substrates, including the apoptotic molecule procaspase 12 and podocyte cytoskeletal protein talin 1. Importantly, a chemical compound, K201, can block RyR2-Ser2808 phosphorylation-mediated ER calcium depletion and podocyte injury in ER-stressed podocytes, as well as inhibit albuminuria in our NS model. In addition, we discovered that mesencephalic astrocyte-derived neurotrophic factor (MANF) can revert defective RyR2-induced ER calcium leak, a bioactivity for this ER stress-responsive protein. Thus, podocyte RyR2 remodeling contributes to ER stress-induced podocyte injury. K201 and MANF could be promising therapies for the treatment of podocyte ER stress-induced NS/FSGS.
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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.