| Thiazolidinediones alter growth and epithelial cell integrity, independent of PPAR{gamma} and MAPK activation, in mouse M1 Cortical Collecting Duct Cells. | |
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MedLine Citation:
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PMID: 20164153 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Peroxisome proliferator-activated receptor (PPAR)-gamma is highly expressed in the collecting duct (CD), yet little is known about the effects of PPARgamma ligands, thiazolidinediones (TZDs), on CD cell structure and function. M1 mouse cortical CD cells were treated with 5 muM troglitazone (TRO) and rosiglitazone (ROSI). First growth was measured by thymidine and H(3)-leucine incorporation, as well as analysis of cyclin D1 and the CDK inhibitor p27 by Western blot. H(3)-thymidine incorporation was reduced by 56 and 24% by TRO and ROSI at 6 hours, and H(3)-leucine by 21 and 10%. A similar growth inhibition was also observed after 24 hours for thymidine, but leucine was reduced by 48 and 24% respectively. Likewise, cyclin D1 was diminished 60% by TRO, and p27 was elevated 1.6 and 1.7-fold in response to TRO and ROSI. Next epithelial cell integrity was assessed by measuring different markers by Western blot analysis. While fibronectin and alpha-smooth muscle actin levels were unchanged, by 24 hours E-cadherin was decreased by 50%, and beta-catenin levels were reduced 2-fold and 1.5-fold in response to TRO and ROSI respectively. GW9662, a PPARgamma antagonist, did not reverse any of the TZD responses in M1 cells. Of interest phosho-p38 levels were also elevated 2-fold in response to TRO and 2.3-fold to ROSI, but MAPK inhibition by PD98059 or SB203580 caused an additive inhibition of cell growth, and did not alter E-cadherin or beta-catenin in response to TZDs. Finally apoptotic death was assessed by Western blot, but cleaved caspase-3 levels were unchanged from 15 min to 24 hours in response to TZDs, and TRO did not affect cell viability or ROS generation. Our data suggest that TZDs cause a disruption of M1 cell integrity that is preceded by an inhibition of cell growth. This response is independent of p38 or PPARgamma activation. Key words: M1 collecting duct cells, Troglitazone, Rosiglitazone, growth. |
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Authors:
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Rania Nasrallah; Jordan Clark; Jaime Corinaldi; Genevieve Paris; Pedro Miura; Bernard J Jasmin; Richard L Hebert |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2010-2-17 |
Journal Detail:
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Title: American journal of physiology. Renal physiology Volume: - ISSN: 1522-1466 ISO Abbreviation: - Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2010-2-18 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901990 Medline TA: Am J Physiol Renal Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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University of Ottawa. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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