有哪些信誉好的足球投注网站a possible contribution of altered cathepsin b expression to the development of skin sclerosis and vasculopathy in systemic sclerosis可能贡献的发展改变了组织蛋白酶b的表达在系统性硬化皮肤硬化和血管病变.pdfVIP
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a possible contribution of altered cathepsin b expression to the development of skin sclerosis and vasculopathy in systemic sclerosis可能贡献的发展改变了组织蛋白酶b的表达在系统性硬化皮肤硬化和血管病变
A Possible Contribution of Altered Cathepsin B
Expression to the Development of Skin Sclerosis and
Vasculopathy in Systemic Sclerosis
Shinji Noda, Yoshihide Asano*, Kaname Akamata, Naohiko Aozasa, Takashi Taniguchi, Takehiro
Takahashi, Yohei Ichimura, Tetsuo Toyama, Hayakazu Sumida, Koichi Yanaba, Yayoi Tada, Makoto
Sugaya, Takafumi Kadono, Shinichi Sato
Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan
Abstract
Cathepsin B (CTSB) is a proteolytic enzyme potentially modulating angiogenic processes and extracellular matrix
remodeling. While matrix metalloproteinases are shown to be implicated in tissue fibrosis and vasculopathy associated with
systemic sclerosis (SSc), the role of cathepsins in this disease has not been well studied. The aim of this study is to evaluate
the roles of CTSB in SSc. Serum pro-CTSB levels were determined by enzyme-linked immunosorbent assay in 55 SSc patients
and 19 normal controls. Since the deficiency of transcription factor Fli1 in endothelial cells is potentially associated with the
development of SSc vasculopathy, cutaneous CTSB expression was evaluated by immunostaining in Fli1+/ 2 and wild type
mice as well as in SSc and control subjects. The effects of Fli1 gene silencing and transforming growth factor-b (TGF-b) on
CTSB expression were determined by real-time PCR in human dermal microvascular endothelial cells (HDMECs) and dermal
fibroblasts, respectively. Serum pro-CTSB levels were significantly higher in limited cutaneous SSc (lcSSc) and late-stage
diffuse cutaneous SSc (dcSSc) patients than in healthy controls. In dcSSc, patients with increased serum pro-CTSB levels
showed a significantly higher frequency of digital ulcers than those with normal levels. CTSB expression in dermal blood
vessels was increased in Fli1+/ 2 mice compared with wild type mice an
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