help button home button Am J Pathol Epitomics
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Quan, T.
Right arrow Articles by Fisher, G. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Quan, T.
Right arrow Articles by Fisher, G. J.
(American Journal of Pathology. 2006;169:482-490.)
© 2006 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2006.060128

Elevated Cysteine-Rich 61 Mediates Aberrant Collagen Homeostasis in Chronologically Aged and Photoaged Human Skin

TaiHao Quan, TianYuan He, Yuan Shao, Lin Lin, Sewon Kang, John J. Voorhees and Gary J. Fisher

From the Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan

Alterations of human skin connective tissue structure and function are prominent features of chronological aging and solar UV irradiation-induced premature aging (photoaging). These skin connective tissue abnormalities result, in part, from reduced synthesis and elevated degradation of type I collagen, the major structural protein in skin. Here, we report that cysteine-rich 61 (CYR61/CCN1), a novel mediator of collagen homeostasis, is predominantly expressed in human skin connective tissue and is significantly elevated in fibroblasts in chronologically aged (80+ years) and photoaged human skin in vivo. In cultured human skin fibroblasts, elevated CYR61 expression substantially reduces type I procollagen and concurrently increases matrix metalloproteinase-1 (MMP-1), which initiates fibrillar collagen degradation. Elevated CYR61 caused down-regulation of transforming growth factor-ß type II receptor mRNA and protein levels, thereby impairing the transforming growth factor-ß pathway, which reduced type I procollagen and raised MMP-1 expression. Furthermore, elevated CYR61 induced transcription factor activator protein-1 (AP-1), which functions to stimulate MMP-1 expression. Thus, elevated expression of CYR61 in human skin fibroblasts acts through multiple pathways to cause alterations of collagen homeostasis similar to those pathways observed in aged human skin in vivo. These data identify CYR61 as a pivotal regulator of collagen production and degradation in aged and photoaged human skin.




This article has been cited by other articles:


Home page
 Am. J. Pathol.Home page
G. J. Fisher, T. Quan, T. Purohit, Y. Shao, M. K. Cho, T. He, J. Varani, S. Kang, and J. J. Voorhees
Collagen Fragmentation Promotes Oxidative Stress and Elevates Matrix Metalloproteinase-1 in Fibroblasts in Aged Human Skin
Am. J. Pathol., January 1, 2009; 174(1): 101 - 114.
[Abstract] [Full Text] [PDF]

Home page
 Arch DermatolHome page
R. Kafi, H. S. R. Kwak, W. E. Schumacher, S. Cho, V. N. Hanft, T. A. Hamilton, A. L. King, J. D. Neal, J. Varani, G. J. Fisher, et al.
Improvement of Naturally Aged Skin With Vitamin A (Retinol)
Arch Dermatol, May 1, 2007; 143(5): 606 - 612.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2006 by the American Society for Investigative Pathology.