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学科主题临床医学
Increased periostin expression affects the proliferation, collagen synthesis, migration and invasion of keloid fibroblasts under hypoxic conditions
Zhang, Zhe; Nie, Fangfei; Kang, Chunfu; Chen, Bin; Qin, Zelian; Ma, Jianxun; Ma, Yongguang; Zhao, Xia
关键词Periostin Hypoxia Fibroblast Keloid Hypoxia-inducible Factor
刊名INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
2014-07-01
DOI10.3892/ijmm.2014.1760
34期:1页:253-261
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Medicine, Research & Experimental
资助者National Natural Science Foundation of China ; Ministry of Education doctoral foundation of the Peoples Republic of China ; National Natural Science Foundation of China ; Ministry of Education doctoral foundation of the Peoples Republic of China
研究领域[WOS]Research & Experimental Medicine
关键词[WOS]HYPERTROPHIC SCARS ; SIGNALING PATHWAYS ; TGF-BETA ; PERIODONTAL-LIGAMENT ; AKT/PKB PATHWAY ; GROWTH-FACTORS ; CELL-SURVIVAL ; CANCER-CELLS ; PROGRESSION ; INHIBITOR
英文摘要

Periostin, a secreted extracellular matrix protein, is involved in the wound healing and pathological process of various human cancers. Keloid scars are fibroproliferative tumor-like lesions and develop under local hypoxia. Using suppression subtractive hybridization, in a previous study, we found that periostin is overexpressed in keloids compared with hypertrophic scars. However, little is known about the regulation and function of periostin in keloids. In this study, we examined the effects of periostin on the bioactivity of keloid fibroblasts (KFs) in order to determine whether periostin is involved in hypoxia-stimulated keloid pathogenesis by measuring the expression levels of periostin in KFs cultured under hypoxic conditions. We also investigated the association between periostin and hypoxia-inducible factor-1 alpha (HIF-1 alpha). The mRNA, intracellular protein and secreted protein level of periostin was examined by RT-PCR (and quantitative PCR), western blot analysis and enzyme-linked immunosorbent assay (ELISA), respectively. We also used shRNA targeting periostin to knockdown its expression in the KFs. We report that hypoxia (2% O-2) upregulates both HIF-1 alpha and periostin expression in KFs. In addition, hypoxia-upregulated periostin expression was regulated by HIF-1 alpha. The inhibition of periostin by short hairpin RNA decreased the hypoxia-stimulated proliferation, collagen synthesis, migration and invasion of KFs and altered the cell cycle, but did not affect apoptosis; treatment with recombinant human periostin protein reversed these effects. Periostin also activated the alpha v beta 3 integrin-PI3K/Akt pathway in the KFs. These findings suggest that hypoxia initiates hyperplasia of KFs and increases periostin expression under hypoxic conditions; periostin is involved in the pathogenesis of keloids, which indicates that periostin may be a novel therapeutic target for keloids and other fibroproliferative disorders.

语种英语
所属项目编号30973126 ; 20130001110095
资助者National Natural Science Foundation of China ; Ministry of Education doctoral foundation of the Peoples Republic of China ; National Natural Science Foundation of China ; Ministry of Education doctoral foundation of the Peoples Republic of China
WOS记录号WOS:000338178000030
引用统计
被引频次:15[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/54699
专题北京大学第三临床医学院_成形外科
作者单位Peking Univ Third Hosp, Dept Plast Surg, Beijing 100191, Peoples R China
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Zhang, Zhe,Nie, Fangfei,Kang, Chunfu,et al. Increased periostin expression affects the proliferation, collagen synthesis, migration and invasion of keloid fibroblasts under hypoxic conditions[J]. INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE,2014,34(1):253-261.
APA Zhang, Zhe.,Nie, Fangfei.,Kang, Chunfu.,Chen, Bin.,Qin, Zelian.,...&Zhao, Xia.(2014).Increased periostin expression affects the proliferation, collagen synthesis, migration and invasion of keloid fibroblasts under hypoxic conditions.INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE,34(1),253-261.
MLA Zhang, Zhe,et al."Increased periostin expression affects the proliferation, collagen synthesis, migration and invasion of keloid fibroblasts under hypoxic conditions".INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 34.1(2014):253-261.
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