Increased expression of heat-shock protein 47 is associated with overproduction of type I procollagen in systemic sclerosis skin fibroblasts.
Heat-shock protein 47 (HSP47) is a collagen-binding stress protein that is thought to act as a collagen-specific molecular chaperon during the biosynthesis and secretion of procollagen. In this study we examined the expression of HSP47 mRNA and protein in systemic sclerosis (SSc) skin fibroblasts. HSP47 mRNA and protein levels were significantly higher in fibroblast cultures from SSc patient-involved skin samples than in fibroblasts from normal skin from healthy individuals, as assessed by northern blot and immunoblot analyses, respectively. SSc cultured fibroblasts with increased levels of HSP47 mRNA and protein showed high expression of type I procollagen. By in situ hybridization, SSc skin had a higher number of fibroblasts with high HSP47 and procollagen alpha1(I) mRNA levels than normal skin, and the distribution of HSP47 mRNA was similar to that of procollagen alpha1(I) mRNA. We also investigated the effects of cytokines on the expression of HSP47 in normal cultured fibroblasts. Transforming growth factor-beta1 and interleukin-4 increased HSP47 mRNA and protein levels, whereas interferon-gamma reduced HSP47 expression. The same pattern of cytokine-regulated expression was observed for type I procollagen levels. These results indicate that HSP47 expression is closely associated with that of type I procollagen in skin fibroblasts, and that increased expression of HSP47 may be involved in the abundant production of type I procollagen by SSc fibroblasts.
Kuroda
K
K
Department of Dermatology, School of Medicine, Chiba University, Japan.
Tsukifuji
R
R
Shinkai
H
H
D002478:Cells, Cultured; D005347:Fibroblasts / Q000737:chemistry* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D015151:Immunoblotting; D017403:In Situ Hybridization; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D011347:Procollagen / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000378:metabolism*; D012867:Skin / Q000166:cytology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D011347:Procollagen; D012333:RNA, Messenger; C494660:SERPINH1 protein, human; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D007371:Interferon-gamma