Accession Number:

ADA510087

Title:

The Modulation of Fibrosis in Scleroderma by 3-deoxyglucosone

Descriptive Note:

Annual rept. 1 Jun 2008-30 May 2009

Corporate Author:

DREXEL UNIV PHILADELPHIA PA

Personal Author(s):

Report Date:

2009-06-01

Pagination or Media Count:

27.0

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. Specifically we found decreased expression of ERK12 and MEK12 phosphorylation, reduction on collagen specific transcription factors, increased adherence to the 3DG-collagen and that 11 integrin is the most important integrin for binding 3DG-collagen. We have found further perturbations in fibroblast signaling with 3DG-collagen, including increased GADD153 expression, p38 MAP kinase and Smad7. These alterations contribute to the decreased expression of collagen. We continue to further unravel the alterations observed in signaling with 3DG.

Subject Categories:

  • Biochemistry
  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE