Open AccessCCN1 contributes to skin connective tissue aging by inducing age‐associated secretory phenotype in human skin dermal fibroblasts
Author(s) -
Quan Taihao,
Qin Zhaoping,
Robichaud Patrick,
Voorhees John J.,
Fisher Gary J.
Publication year - 2011
Publication title -
journal of cell communication and signaling
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 44
eISSN - 1873-961X
pISSN - 1873-9601
DOI - 10.1007/s12079-011-0144-0
Subject(s) - dermis , microbiology and biotechnology , connective tissue , human skin , extracellular matrix , matrix metalloproteinase , secretion , phenotype , proinflammatory cytokine , chemistry , homeostasis , in vivo , matricellular protein , biology , immunology , pathology , inflammation , medicine , biochemistry , genetics , gene
Dermal connective tissue collagen is the major structural protein in skin. Fibroblasts within the dermis are largely responsible for collagen production and turnover. We have previously reported that dermal fibroblasts, in aged human skin in vivo, express elevated levels of CCN1, and that CCN1 negatively regulates collagen homeostasis by suppressing collagen synthesis and increasing collagen degradation (Quan et al. Am J Pathol 169:482–90, 2006, J Invest Dermatol 130:1697–706, 2010). In further investigations of CCN1 actions, we find that CCN1 alters collagen homeostasis by promoting expression of specific secreted proteins, which include matrix metalloproteinases and proinflammatory cytokines. We also find that CCN1‐induced secretory proteins are elevated in aged human skin in vivo. We propose that CCN1 induces an “Age‐Associated Secretory Phenotype”, in dermal fibroblasts, which mediates collagen reduction and fragmentation in aged human skin.