The Modulation of Fibrosis In Scleroderma by 3-Deoxyglucosone

Abstract

Scleroderma is a disease where excess collagen is deposited in the skin and internal organs. The tissues become hard and in the end fail to function. To date there is no cure, nor is there an effective therapy that will control the deposition of the collagen. The goals of this application were to investigate the cellular signaling within fibroblasts that were mediated by the glycation end product, 3DG. We find that 3DG decreases the expression of collagens and therefore we proposed to understand the cellular signaling in fibroblasts in response to this compound. 3DG-collagen induced ER stress leading to caspase 3 activation, and decreased cell proliferation. Furthermore, 3DG-collagen induced changes in integrins and growth factor expression. Furthermore, we found that p38 MAPK was a crucial protein that regulated whether the fibroblast responded to a stress signal or a growth signal. The data obtained from this grant has allowed us to identify two candidate chemicals that lower collagen expression by SSc fibroblasts.

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Document Details

Document Type
Technical Report
Publication Date
Jun 01, 2011
Accession Number
ADA561077

Entities

People

  • Carol Artlett

Organizations

  • Drexel University

Tags

DTIC Thesaurus Topics

  • Adhesion
  • Apoptosis
  • Cell Movement
  • Cell Physiological Processes
  • Cells
  • Cellular Structures
  • Chemistry
  • Diseases And Disorders
  • Free Radicals
  • Growth Factors
  • Microscopes
  • Muscle Cells
  • Oxidative Stress
  • Peptide Growth Factors
  • Proteins
  • Vitamin C
  • Wound Healing

Fields of Study

  • Biology

Readers

  • Immunology and Pathology
  • Molecular Biology and Genetics