ArticleInternational urology and nephrology2019
Increased levels of serum pigment epithelium-derived factor aggravate proteinuria via induction of podocyte actin rearrangement.
Article in International urology and nephrology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 12 citations in OpenAlex.
- Proteomics and Incident Kidney Failure in Individuals With CKD: The African American Study of Kidney Disease and Hypertension and the Boston Kidney Biopsy Cohort.Kidney medicine · 2024Article
- The Various Roles of PEDF in Cancer.Cancers · 2024Review
- C1q/TNF-Related Protein-3 (CTRP-3) and Pigment Epithelium-Derived Factor (PEDF) Concentrations in Patients with Gestational Diabetes Mellitus: A Case-Control Study.Journal of clinical medicine · 2020Article
- The Rab-Rabphilin system in injured human podocytes stressed by glucose overload and angiotensin II.American journal of physiology. Renal physiology · 2020Article
- Comparative proteomic analysis of renal proteins from IgA nephropathy model mice and control mice.Clinical and experimental nephrology · 2020Article
- Role of Transient Receptor Potential Canonical Channel 6 (TRPC6) in Diabetic Kidney Disease by Regulating Podocyte Actin Cytoskeleton Rearrangement.Journal of diabetes research · 2020Review
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
purposeTo assess the role of serum pigment epithelium-derived factor (PEDF) in the occurrence and development of proteinuria and renal dysfunction and determine its relevant signaling pathway.
methodsWe analyzed serum PEDF, creatinine, the urinary albumin-to-creatinine ratio, and renal morphology of normal or streptozotocin (STZ)-induced diabetic mice, before and after treatment with PEDF. In vitro, podocytes were stimulated with PEDF under normal or high-glucose conditions; permeability was measured by the transwell assay with fluorescein isothiocyanate (FITC)-dextran; and F-actin cytoskeleton was analyzed by phalloidin staining. Apoptosis was assessed by flow cytometry. RhoA activity and ROCK1, ZO-1, nephrin, and podocin levels were detected by Western blotting.
resultsDiabetic mice exhibited a high serum PEDF level. In vivo, elevated serum PEDF led to proteinuria, increased serum creatinine, and podocyte foot process fusion in normal or diabetic mice. In vitro, both high-glucose and PEDF stimulation activated the RhoA/ROCK1 pathway in podocytes and promoted cell permeability, F-actin rearrangement, and apoptosis. Inhibition of RhoA/ROCK1 alleviated the damage from these effects.
conclusionsElevated serum PEDF aggravates the development of proteinuria and renal dysfunction by inducing F-actin arrangement, foot process fusion, and apoptosis of podocytes in both normal and diabetic mice, and this effect may be mediated by activation of the RhoA/ROCK1 pathway.
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