Skip to content Skip to navigation
University of Warwick
  • Study
  • |
  • Research
  • |
  • Business
  • |
  • Alumni
  • |
  • News
  • |
  • About

University of Warwick
Publications service & WRAP

Highlight your research

  • WRAP
    • Home
    • Search WRAP
    • Browse by Warwick Author
    • Browse WRAP by Year
    • Browse WRAP by Subject
    • Browse WRAP by Department
    • Browse WRAP by Funder
    • Browse Theses by Department
  • Publications Service
    • Home
    • Search Publications Service
    • Browse by Warwick Author
    • Browse Publications service by Year
    • Browse Publications service by Subject
    • Browse Publications service by Department
    • Browse Publications service by Funder
  • Help & Advice
University of Warwick

The Library

  • Login
  • Admin

Inhibition of host connective tissue growth factor expression : a novel Trypanosoma cruzi-mediated response

Tools
- Tools
+ Tools

Unnikrishnan, Meera and Burleigh, Barbara A. (2004) Inhibition of host connective tissue growth factor expression : a novel Trypanosoma cruzi-mediated response. The FASEB Journal, Volume 18 (Number 14). pp. 1625-1635. doi:10.1096/fj.04-1554com ISSN 0892-6638.

Research output not available from this repository.

Request-a-Copy directly from author or use local Library Get it For Me service.

Official URL: http://dx.doi.org/10.1096/fj.04-1554com

Request Changes to record.

Abstract

Connective tissue growth factor (CTGF) is a secreted cytokine that plays a fundamental role in the development of tissue fibrosis by mediating many of the profibrotic effects of TGF-β. We present the novel finding that the intracellular pathogen Trypanosoma cruzi elicits immediate and sustained repression of basal CTGF expression in dermal fibroblasts, followed by down-regulation of the extracellular matrix proteins, fibronectin, and collagen I α1. To address mechanisms underlying this response, the major CTGF-regulating pathways were investigated. We report that both T. cruzi trypomastigotes and secreted parasite factor(s) antagonize TGF-β-dependent induction of CTGF in fibroblasts. Of the TGF-β-dependent signaling pathways required for CTGF expression, we demonstrate that T. cruzi interferes with cellular Erk1/2 phosphorylation but not Smad3 signaling. While increased stimulation of Erk phosphorylation alone was insufficient to override the parasite-mediated repression of CTGF, stimulation of fibroblasts with increased concentrations of TGF-β, which activates both Smad3 and Erk1/2, completely abrogated this inhibition. Together with the finding that T. cruzi-mediated down-regulation of CTGF expression requires de novo host cell protein synthesis, our data indicate that the unique ability of T. cruzi to interfere with the host fibrogenic response is a complex process requiring input from multiple host cell signaling pathways.—Unnikrishnan, M., Burleigh, B. A. Inhibition of host connective tissue growth factor expression: a novel Trypanosoma cruzi-mediated response.

Item Type: Journal Article
Subjects: Q Science > QP Physiology
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Microbiology & Infection
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): Trypanosoma cruzi, Extracellular matrix, Mitogen-activated protein kinases, Connective tissues -- Growth
Journal or Publication Title: The FASEB Journal
Publisher: Federation of American Societies for Experimental Biology
ISSN: 0892-6638
Official Date: November 2004
Dates:
DateEvent
November 2004Published
Volume: Volume 18
Number: Number 14
Page Range: pp. 1625-1635
DOI: 10.1096/fj.04-1554com
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access
Funder: American Heart Association (AHA), National Institutes of Health (U.S.) (NIH), Burroughs Wellcome Fund (BWF)
Grant number: AI47960 and HL073227 (NIH)

Request changes or add full text files to a record

Repository staff actions (login required)

View Item View Item
twitter

Email us: wrap@warwick.ac.uk
Contact Details
About Us