| Glucocorticoids protect and enhance recovery of cultured murine podocytes via actin filament stabilization. | |
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MedLine Citation:
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PMID: 16316324 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Nephrotic syndrome is a common kidney disease in both children and adults that is characterized by dramatic structural changes in the actin-rich foot processes of glomerular podocytes. Although glucocorticoids are the primary treatment for nephrotic syndrome, neither the target cell nor mechanism of action of glucocorticoids in nephrotic syndrome is known. For the last 30 years glucocorticoids have been presumed to act by reducing the release of soluble mediators of disease by circulating lymphocytes. In contrast, we hypothesized that glucocorticoids exert their beneficial effects in nephrotic syndrome by direct action on podocytes. METHODS: Cultured murine podocytes were treated with glucocorticoids in the presence and absence of mifepristone (to inhibit glucocorticoid-induced transcriptional activation) and challenged using our previously reported in vitro model of puromycin aminonucleoside (PAN)-induced podocyte injury, as well as by direct disruption of actin filaments with latrunculin and cytochalasin. Cell viability, actin filament distribution, total polymerized actin content, and actin-regulating guanine triphosphatase (GTPase) activities were measured. RESULTS: We demonstrated that treatment of cultured murine podocytes with the glucocorticoid dexamethasone both protected and enhanced recovery from PAN-induced injury. Dexamethasone also increased total cellular polymerized actin, stabilized actin filaments against disruption by PAN, latrunculin, or cytochalasin, and induced a significant increase in the activity of the actin-regulating GTPase RhoA. CONCLUSION: These data suggest that, contrary to the current therapeutic paradigm, the beneficial effects of glucocorticoids in nephrotic syndrome may result, at least in part, from direct effects on podocytes leading to enhanced actin filament stability. |
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Authors:
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Richard F Ransom; Nancy G Lam; Mark A Hallett; Simon J Atkinson; William E Smoyer |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Kidney international Volume: 68 ISSN: 0085-2538 ISO Abbreviation: Kidney Int. Publication Date: 2005 Dec |
Date Detail:
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Created Date: 2005-11-30 Completed Date: 2006-02-01 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0323470 Medline TA: Kidney Int Country: United States |
Other Details:
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Languages: eng Pagination: 2473-83 Citation Subset: IM |
Affiliation:
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Pediatric Nephrology Division, University of Michigan, Ann Arbor, MI 48109, USA. rransom@umich.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anti-Inflammatory Agents / pharmacology* Antibiotics, Antineoplastic / pharmacology Bicyclo Compounds, Heterocyclic / pharmacology Cell Line, Transformed Cell Survival / drug effects Cytochalasin D / pharmacology Dexamethasone / pharmacology* Drug Interactions Hormone Antagonists / pharmacology Mesangial Cells / cytology, drug effects, metabolism Mice Microfilaments / drug effects*, metabolism Mifepristone / pharmacology NIH 3T3 Cells Nucleic Acid Synthesis Inhibitors / pharmacology Podocytes / cytology*, drug effects*, metabolism Polymers / metabolism Puromycin Aminonucleoside / pharmacology Thiazoles / pharmacology Thiazolidines rho GTP-Binding Proteins / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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DK53194/DK/NIDDK NIH HHS; K08 DK02455-01/DK/NIDDK NIH HHS; R01 DK55602/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anti-Inflammatory Agents; 0/Antibiotics, Antineoplastic; 0/Bicyclo Compounds, Heterocyclic; 0/Hormone Antagonists; 0/Nucleic Acid Synthesis Inhibitors; 0/Polymers; 0/Thiazoles; 0/Thiazolidines; 22144-77-0/Cytochalasin D; 50-02-2/Dexamethasone; 58-60-6/Puromycin Aminonucleoside; 76343-93-6/latrunculin A; 84371-65-3/Mifepristone; EC 3.6.5.2/rho GTP-Binding Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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