IGF-binding protein mRNAs in the human fetus: Tissue and cellular distribution of developmental expression
IGF-binding protein mRNAs in the human fetus: Tissue and cellular distribution of developmental expression
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DOI：
10.1159/000184780
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发表时间：
1996-01-01
期刊：
影响因子：
--
通讯作者：
Nygard, K
中科院分区：
文献类型：
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作者：
Han, VKM;Matsell, DG;Nygard, K
胰岛素样生长因子（IGF-I和IGF-II）由大多数胚胎和胎儿组织合成，并作为自分泌/旁分泌因子调节细胞生长和分化。一个家族的六个IGF结合蛋白（IGFBPs）调节IGF的生物学行为作为负（抑制）和正（增强）调制器。为了确定IGFBP mRNA表达的组织分布，我们进行了北方印迹分析和原位杂交的人胎儿组织在胎龄10-16周（n = 8）。IGFBP-1 mRNA仅在肝脏中表达，而其他IGFBP mRNA在检查的每个组织中以可变丰度表达。IGFBP-2 mRNA在每个组织中以中等丰度表达，在肝脏中观察到最高水平; IGFBP-3 mRNA在皮肤、肌肉和心脏中表达最丰富; IGFBP-4 mRNA在所有组织中以中等丰度表达; IGFBP-5 mRNA在皮肤、肌肉和胃中表达最丰富，IGFBP-6 mRNA在所有组织中以低丰度表达。值得注意的例外是肝脏表达很少或没有IGFBP-4、-5和-6 mRNA，脾脏和胸腺表达低水平的IGFBP-5 mRNA，脑表达很少或没有IGFBP-5和IGFBP-6 mRNA。人胎儿组织的原位杂交显示，IGFBP mRNA在上皮细胞和间充质细胞中表达，这取决于特定的IGFBP和发育阶段。IGFBP-3、IGFBP-4和IGFBP-5 mRNA主要定位于间充质细胞，IGFBP-2 mRNA主要定位于上皮细胞。IGFBP-6 mRNA在上皮细胞和间充质细胞中均以低丰度定位。这些研究表明，IGFBPs是重要的旁分泌调节剂的IGF对细胞生长和分化的作用，通过调节IGF依赖或IGF非依赖的行动。
Insulin-like growth factors (IGF-I and IGF-II) are synthesized by most embryonic and fetal tissues, and regulate cellular growth and differentiation as autocrine/paracrine factors. A family of six IGF-binding proteins (IGFBPs) modulate IGF biological actions as both negative (inhibitory) and positive (potentiating) modulators. To determine the tissue distribution of IGFBP mRNA expression, we performed Northern blot analysis and in situ hybridization of human fetal tissues during gestational ages 10-16 weeks (n = 8). IGFBP-1 mRNA was expressed only :in the liver, whereas other IGFBP mRNAs were expressed in variable abundance in every tissue examined. IGFBP-2 mRNA was expressed in moderate abundance in every tissue with the highest level observed in the liver; IGFBP-3 mRNA was expressed most abundantly in the skin, muscle and heart; IGFBP-4 mRNA was expressed in moderate abundance equally in all tissues; IGFBP-5 mRNA was expressed most abundantly in the skin, muscle and stomach, and IGFBP-6 mRNA was expressed in low abundance in all tissues. Notable exceptions were that liver expressed little or no IGFBP-4, -5 and -6 mRNAs, spleen and thymus expressed low levels of IGFBP-5 mRNA, and brain expressed little or no IGFBP-5 and IGFBP-6 mRNA. In situ hybridization of human fetal tissues showed IGFBP mRNAs were expressed in both epithelial and mesenchymal cells depending on the specific IGFBP and the stage of development. IGFBP-3, -4, and -5 mRNAs were localized mainly in the mesenchymal cells, and IGFBP-2 mRNA was localized predominantly in the epithelial cells. IGFBP-6 mRNA was localized in low abundance in both epithelial and mesenchymal cells. These studies indicate that IGFBPs are important paracrine modulators of IGF action on cellular growth and differentiation, by modulating IGF-dependent or IGF-independent actions.