Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Molecular Pharmacology
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Molecular Pharmacology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

Comparison of Direct Action of Thiazolidinediones and Glucocorticoids on Renal Podocytes: Protection from Injury and Molecular Effects

Shipra Agrawal, Adam J. Guess, Rainer Benndorf and William E. Smoyer
Molecular Pharmacology September 2011, 80 (3) 389-399; DOI: https://doi.org/10.1124/mol.111.071654
Shipra Agrawal
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Adam J. Guess
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rainer Benndorf
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
William E. Smoyer
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

The U.S. Food and Drug Administration-approved thiazolidinediones pioglitazone and rosiglitazone are peroxisome proliferator-activated receptor-γ (PPARγ) agonists developed to control serum glucose in patients with diabetes. They have been found to reduce proteinuria and microalbuminuria in both diabetic nephropathy and nondiabetic glomerulosclerosis. We hypothesized that the renal protective effects of thiazolidinediones result, at least in part, from their direct action on podocytes, similar to glucocorticoids. Treatment with pioglitazone, rosiglitazone, or dexamethasone significantly protected podocytes against puromycin aminonucleoside-induced injury (designed to mimic nephrotic syndrome-related injury), as determined by both cell survival and actin cytoskeletal integrity. Furthermore, we compared the ability of these drugs to modulate key signaling pathways in podocytes that may be critical to their protective effects. Rosiglitazone deactivated the mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinases 1/2, p38 MAPK, and stress-activated protein kinase/c-Jun NH2-terminal kinase, whereas pioglitazone did not, and dexamethasone deactivated to some extent. Similar to dexamethasone, both thiazolidinediones increased the glucocorticoid receptor phosphorylation, and this response to rosiglitazone and possibly to pioglitazone was PPARγ-dependent. Furthermore, both drugs mimicked or enhanced the effects of dexamethasone on glucocorticoid-responsive genes in a PPARγ- and glucocorticoid receptor-dependent manner. In addition, both thiazolidinediones mimicked dexamethasone-induced effects on calcineurin activity. In summary, thiazolidinediones are able to modulate the glucocorticoid pathway and exert direct protective effects on podocytes, similar to glucocorticoids. This suggests that thiazolidinediones may have potential clinical utility as either primary or adjunctive therapy for nephrotic syndrome or other diseases treated with glucocorticoids. These findings may also lend mechanistic insight into the well established but poorly understood renal protective effects of thiazolidinediones in diabetic nephropathy.

Footnotes

  • This work was supported in part by the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [Grants R01-DK077283, R56-DK55602].

  • Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.

    doi:10.1124/mol.111.071654.

  • ABBREVIATIONS:

    PPARγ
    peroxisome proliferator-activated receptor γ
    CaN
    calcineurin
    CORT108297
    (R)-4a-ethoxy-1-(4-fluorophenyl)-6-(4-trifluoromethylbenzenesulfonyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triazacylopenta[b]naphthalene
    DAPI
    4′,6-diamidino-2-phenylindole
    Dex
    dexamethasone
    ERK1/2
    extracellular signal-regulated kinase 1/2
    FBS
    fetal bovine serum
    FDA
    U.S. Food and Drug Administration
    GC
    glucocorticoid
    GR
    glucocorticoid receptor
    GRE
    glucocorticoid-responsive element
    GW9662
    2-Chloro-5-nitro-N-phenylbenzamide
    MAPK
    mitogen-activated protein kinase
    NS
    nephrotic syndrome
    O/N
    overnight
    PCR
    polymerase chain reaction
    RT-PCR
    reverse transcription-polymerase chain reaction
    PAN
    puromycin aminonucleoside
    PBS
    phosphate-buffered saline
    PBS-T
    PBS containing 0.1% Tween 20
    Pio
    pioglitazone
    Rosi
    rosiglitazone
    RU486
    11β-(4-dimethylamino)phenyl-17β-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one
    SAPK/JNK
    stress activated protein kinase/c-Jun N-terminal kinase
    PAGE
    polyacrylamide gel electrophoresis
    TZD
    thiazolidinedione
    MTT
    3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
    MAPK
    mitogen-activated protein kinase
    HEK
    human embryonic kidney
    GAPDH
    glyceraldehyde-3-phosphate dehydrogenase
    FK506
    tacrolimus
    PP
    protein phosphatase
    GW9662
    2-chloro-5-nitrobenzanilide.

  • Received February 9, 2011.
  • Accepted June 2, 2011.
  • Copyright © 2011 The American Society for Pharmacology and Experimental Therapeutics
View Full Text

MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Molecular Pharmacology: 80 (3)
Molecular Pharmacology
Vol. 80, Issue 3
1 Sep 2011
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Pharmacology article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Comparison of Direct Action of Thiazolidinediones and Glucocorticoids on Renal Podocytes: Protection from Injury and Molecular Effects
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Comparison of Direct Action of Thiazolidinediones and Glucocorticoids on Renal Podocytes: Protection from Injury and Molecular Effects

Shipra Agrawal, Adam J. Guess, Rainer Benndorf and William E. Smoyer
Molecular Pharmacology September 1, 2011, 80 (3) 389-399; DOI: https://doi.org/10.1124/mol.111.071654

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleArticle

Comparison of Direct Action of Thiazolidinediones and Glucocorticoids on Renal Podocytes: Protection from Injury and Molecular Effects

Shipra Agrawal, Adam J. Guess, Rainer Benndorf and William E. Smoyer
Molecular Pharmacology September 1, 2011, 80 (3) 389-399; DOI: https://doi.org/10.1124/mol.111.071654
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Authorship Contributions
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Fatty acid amide hydrolase in cisplatin nephrotoxicity
  • eCB Signaling System in hiPSC-Derived Neuronal Cultures
  • Benzbromarone relaxes airway smooth muscle via BK activation
Show more Articles

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About Molecular Pharmacology
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics