Tanaka Nobuyoshi, Masamura Katsuhiko, Yoshida Masahiro, Kato Masayuki, Kawai Yasuyuki, Miyamori Isamu
Third Department of Internal Medicine, Fukui Medical University, Matsuoka-cho, Japan.
Biochem Biophys Res Commun. 2002 Sep 20;297(2):375-81. doi: 10.1016/s0006-291x(02)02197-6.
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.
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。