| Temporal analysis of signaling pathways activated in a murine model of two-kidney, one-clip hypertension. | |
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MedLine Citation:
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PMID: 19625373 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Unilateral renal artery stenosis (RAS) leads to atrophy of the stenotic kidney and compensatory enlargement of the contralateral kidney. Although the two-kidney, one-clip (2K1C) model has been extensively used to model human RAS, the cellular responses in the stenotic and contralateral kidneys, particularly in the murine model, have received relatively little attention. We studied mice 2, 5, and 11 wk after unilateral RAS. These mice became hypertensive within 1 wk. The contralateral kidney increased in size within 2 wk after surgery. This enlargement was associated with a transient increase in expression of phospho-extracellular signal-regulated kinase (p-ERK), the proliferation markers proliferating cell nuclear antigen and Ki-67, the cell cycle inhibitors p21 and p27, and transforming growth factor-beta, with return to baseline levels by 11 wk. The size of the stenotic kidney was unchanged at 2 wk but progressively decreased between 5 and 11 wk. Unlike the contralateral kidney, which showed minimal histopathological alterations, the stenotic kidney developed progressive interstitial fibrosis, tubular atrophy, and interstitial inflammation. Surprisingly, the stenotic kidney showed a proliferative response, which involved largely tubular epithelial cells. The atrophic kidney had little evidence of apoptosis, despite persistent upregulation of p53; expression of cell cycle regulatory proteins in the stenotic kidney was persistently increased through 11 wk. These studies indicate that in the 2K1C model, the stenotic kidney and contralateral, enlarged kidney exhibit a distinct temporal expression of proteins involved in cell growth, cell survival, apoptosis, inflammation, and fibrosis. Notably, an unexpected proliferative response occurs in the stenotic kidney that undergoes atrophy. |
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Authors:
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Jingfei Cheng; Wei Zhou; Gina M Warner; Bruce E Knudsen; Vesna D Garovic; Catherine E Gray; Lilach O Lerman; Jeffrey L Platt; J Carlos Romero; Stephen C Textor; Karl A Nath; Joseph P Grande |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2009-07-22 |
Journal Detail:
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Title: American journal of physiology. Renal physiology Volume: 297 ISSN: 1522-1466 ISO Abbreviation: Am. J. Physiol. Renal Physiol. Publication Date: 2009 Oct |
Date Detail:
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Created Date: 2009-09-29 Completed Date: 2009-10-27 Revised Date: 2011-04-28 |
Medline Journal Info:
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Nlm Unique ID: 100901990 Medline TA: Am J Physiol Renal Physiol Country: United States |
Other Details:
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Languages: eng Pagination: F1055-68 Citation Subset: IM |
Affiliation:
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Department of Experimental Pathology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Actins
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metabolism Animals Apoptosis Atrophy Cell Proliferation Chemokine CCL2 / metabolism Collagen / metabolism Cyclin-Dependent Kinase Inhibitor p21 / metabolism Cyclin-Dependent Kinase Inhibitor p27 / metabolism Cyclins / metabolism Extracellular Signal-Regulated MAP Kinases / metabolism Fibrosis Hyperplasia Hypertension, Renovascular / genetics, metabolism*, pathology Hypertrophy Interphase Kidney / pathology Male Mice Mice, Inbred C57BL Signal Transduction* Time Factors Transforming Growth Factor beta1 / metabolism Tumor Suppressor Protein p53 / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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DK16105/DK/NIDDK NIH HHS; DK47060/DK/NIDDK NIH HHS; HL52297/HL/NHLBI NIH HHS; HL79067/HL/NHLBI NIH HHS; HL85307/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Actins; 0/Ccl2 protein, mouse; 0/Chemokine CCL2; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/Transforming Growth Factor beta1; 0/Tumor Suppressor Protein p53; 0/alpha-smooth muscle actin, mouse; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; 9007-34-5/Collagen; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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