Smad3-dependent regulation of type I collagen in human dermal fibroblasts: Impact on human skin connective tissue aging

Abstract

Thinning of the skin, a prominent feature in aged human skin, significantly impairs skin’s structural integrity and function [ [1] Uitto J. Bernstein E.F. Molecular mechanisms of cutaneous aging: connective tissue alterations in the dermis. J. Investig. Dermatol. Symp. Proc. 1998; 3: 41-44 Abstract Full Text PDF PubMed Scopus (115) Google Scholar ]. Loss of type I collagen, the major structural component in human skin, is largely responsible for age-related thinning of the skin [ [2] Quan T. Fisher G.J. Role of age-associated alterations of the dermal extracellular matrix microenvironment in human skin aging: a mini-review. Gerontology. 2015; PubMed Google Scholar ]. We previously reported that impaired TGF-β signaling, the major regulator of collagen biosynthesis, contributes to collagen-loss in aged human skin [ 3 Quan T. et al. Reduced expression of connective tissue growth factor (CTGF/CCN2) mediates collagen loss in chronologically aged human skin. J. Invest. Dermatol. 2010; 130: 415-424 Abstract Full Text Full Text PDF PubMed Scopus (148) Google Scholar , 4 Quan T. et al. Solar ultraviolet irradiation reduces collagen in photoaged human skin by blocking transforming growth factor-beta type II receptor/Smad signaling. Am. J. Pathol. 2004; 165: 741-751 Abstract Full Text Full Text PDF PubMed Scopus (291) Google Scholar ]. However, it is not known whether, or which Smad proteins are involved in age-related collagen deficit in human skin. This study was thus undertaken to determine the specific Smad proteins that regulate type I procollagen, and further explored the potential mechanisms of loss of type I collagen in aging human skin in vivo.