Fibroblast growth factor-binding protein and N-deacetylase/N-sulfotransferase-1 expression in type II cells is modulated by heparin and extracellular matrix.
Fibroblast growth factor-binding protein and N-deacetylase/N-sulfotransferase-1 expression in type II cells is modulated by heparin and extracellular matrix.
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II 型细胞中成纤维细胞生长因子结合蛋白和 N-脱乙酰酶/N-磺基转移酶-1 的表达受肝素和细胞外基质的调节。
DOI：
10.1152/ajplung.00211.2007
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发表时间：
2007
期刊：
影响因子：
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通讯作者：
Sannes,PhilipL
中科院分区：
文献类型：
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作者：
Newman,DonnaR;Walsh,Eric;Apparao,KBC;Sannes,PhilipL
成纤维细胞生长因子（FGF）在肺损伤或疾病后的发育、维持和修复中起关键作用。它们的活性受多种因素调节，包括FGF结合蛋白（FGF-BP; HBp-17）和N-脱乙酰基酶/N-磺基转移酶-1（NDST-1）。在功能上，FGF-BP将FGF从ECM中的结合位点穿梭到细胞表面并增强FGF结合和信号传导，而NDST-1将硫酸基团添加到FGF辅助受体蛋白聚糖并调节肺泡II型（ATII）细胞成熟和分化。由于ECM的硫酸化性质是其与FGF关系的关键决定因素，因此我们预测ECM及其硫酸化将调节FGF-BP和NDST-1的表达。为了检验这个问题，通过用肝素或氯酸钠（硫酸化抑制剂）处理24-96小时来操纵大鼠ATII细胞的选定培养条件[有和没有与大鼠肺成纤维细胞（RLF）共培养]。此外，ECMs生物合成的RLF长达10天，然后共培养被用作模型干预肺泡细胞和成纤维细胞之间的通信障碍。ATII细胞与RLF细胞共培养后FGF-BP表达增强，而肝素对ATII细胞FGF-BP表达的抑制作用最小。ATII细胞中NDST-1的表达对培养基和ECM中的硫酸化量最敏感，并通过完全硫酸化肝素增强。预制ECM似乎提供了改变后续治疗效果的因素。这些结果表明，在基因表达水平上，硫酸化ECM和成纤维细胞对FGF-BP和NDST-1具有潜在的重要调节作用。
Fibroblast growth factors (FGFs) play critical roles in development, maintenance, and repair following injury or disease in the lung. Their activity is modulated by a variety of factors, including FGF-binding protein (FGF-BP; HBp-17) andN-deacetylase/N-sulfotransferase-1 (NDST-1). Functionally, FGF-BP shuttles FGFs from binding sites in ECMs to cell surfaces and enhances FGF binding and signaling, whereas NDST-1 adds sulfate groups to FGF coreceptor proteoglycans and modulates alveolar type II (ATII) cell maturation and differentiation. Since the sulfated nature of ECMs is a critical determinant of their relationship with FGFs, we predicted that ECMs and their sulfation would modulate the expression of FGF-BP and NDST-1. To examine this question, selected culture conditions of rat ATII cells were manipulated [with and without coculture with rat lung fibroblasts (RLFs)] by treatment with heparin or sodium chlorate (inhibitor of sulfation) for 24–96 h. In addition, ECMs biosynthesized by RLFs for up to 10 days before coculture were used as model intervening barriers to communication between alveolar cells and fibroblasts. FGF-BP expression was enhanced in ATII cells by coculture with RLF cells and least suppressed by desulfated heparin. NDST-1 expression in ATII cells was most sensitive to the amount of sulfation in medium and ECM and enhanced by fully sulfated heparin. Preformed ECM appears to supply factors that modify subsequent treatment effects. These results demonstrate a potentially important modulatory influence of sulfated ECMs and fibroblasts on FGF-BP and NDST-1 at the gene expression level.