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肝素结合表皮生长因子样生长因子在心肌梗死后心脏重塑中的作用。

A role of heparin-binding epidermal growth factor-like growth factor in cardiac remodeling after myocardial infarction.

作者信息

Tanaka Nobuyoshi, Masamura Katsuhiko, Yoshida Masahiro, Kato Masayuki, Kawai Yasuyuki, Miyamori Isamu

机构信息

Third Department of Internal Medicine, Fukui Medical University, Matsuoka-cho, Japan.

出版信息

Biochem Biophys Res Commun. 2002 Sep 20;297(2):375-81. doi: 10.1016/s0006-291x(02)02197-6.

Abstract

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is known to induce cell growth in various cell types via transactivation of epidermal growth factor receptor (EGFR). To investigate the involvement of HB-EGF and EGFR in cardiac remodeling after myocardial infarction (MI), we examined the expressions of mRNA and protein in rat hearts 6 weeks after MI-induction. Where increased expressions of HB-EGF mRNA and protein were observed, infarcted myocardium was replaced by extracellular matrix and interstitial fibroblasts. EGFR mRNA and protein expression did not show significant changes in sham-operated heart tissues, non-infarcted region, and infarcted region. In vitro study demonstrated that HB-EGF mRNA was expressed mainly in cultured fibroblasts rather than in myocytes. We suggest that the interaction between HB-EGF and EGFR transactivation is closely related to the proliferation of cardiac fibroblasts and cardiac remodeling after MI in an autocrine, paracrine, and juxtacrine manner.

摘要

肝素结合表皮生长因子样生长因子(HB-EGF)已知可通过表皮生长因子受体(EGFR)的反式激活在多种细胞类型中诱导细胞生长。为了研究HB-EGF和EGFR在心肌梗死(MI)后心脏重塑中的作用,我们检测了MI诱导后6周大鼠心脏中mRNA和蛋白质的表达。在观察到HB-EGF mRNA和蛋白质表达增加的部位,梗死心肌被细胞外基质和间质成纤维细胞取代。EGFR mRNA和蛋白质表达在假手术心脏组织、非梗死区域和梗死区域未显示出显著变化。体外研究表明,HB-EGF mRNA主要在培养的成纤维细胞中表达,而不是在心肌细胞中表达。我们认为,HB-EGF与EGFR反式激活之间的相互作用以自分泌、旁分泌和近分泌方式与MI后心脏成纤维细胞的增殖和心脏重塑密切相关。

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