期刊文献+

感觉神经肽P物质对肉芽组织成纤维细胞表达表皮生长因子与成纤维细胞生长因子-2及受体的调控作用 被引量:10

Sensory neuropeptide SP modulating expression of EGF,FGF-2 and their receptors in fibroblasts of granulation in vivo and in vitro
原文传递
导出
摘要 目的 从基因水平探讨感觉神经肽SP对肉芽组织成纤维细胞表达表皮生长因子(EGF)、成纤维细胞生长因子 2 (FGF 2 )及受体的调控作用。方法 由在体和离体实验两部分组成。在体实验采用Wistar大鼠 5 0只 ,随机分为辣椒素组和对照组。辣椒素组大鼠皮下注射辣椒素 5 0mg/kg毁损感觉神经 ,1周后行皮肤全层切割伤 ,采用免疫组化结合图像分析 ,观察伤后 3~ 12d伤口肉芽组织内神经肽P物质 (SP)含量。采用原位杂交方法观察EGF、表皮生长因子受体 (EGFR)、FGF 2、成纤维细胞生长因子受体 1(FGFR 1)的基因表达 ,对照组除不化学毁损感觉神经外 ,余处理同辣椒素组。离体实验采用RT PCR技术观察不同浓度 (10 -9~ 10 -5mol/L)SP作用于培养肉芽组织成纤维细胞后 ,上述生长因子及受体的表达。结果 在体实验示 ,肉芽组织SP免疫阳性染色与EGF、FGF 2及其受体表达有关 ,化学毁损感觉神经 ,肉芽组织SP免疫阳性染色减弱 ,上述因子及受体的表达也明显抑制。离体实验发现 ,上调培养肉芽组织成纤维细胞内源性EGF和EGFRmRNA表达的SP浓度为 10 -8~10 -6mol/L和 10 -6~ 10 -5mol/L ,上调FGF 2和FGFR 1mRNA表达的SP浓度分别为 10 -9~ 10 -5mol/L和 10 -6~ 10 -5mol/L。结论 伤口愈合中 ,感觉神经释放的SP参与肉芽组织成纤维? Objective To study the modulating effect of sensory neuropeptide substance P (SP) on gene expression of epidermal growth factor(EGF), fibroblast growth factor-2(FGF-2) and EGF receptor(EGFR), FGF receptor-1(FGFR-1) in granulation fibroblast. Methods The study consisted of two parts, in vivo and in vitro. In vivo, fifty wistar rats were randomly arranged into capsaicin group and control group. The rats in capsaicin group were subcutaneously injected with neurotoxin dose of capsaicin (50 mg/kg) on the back of the rats to chemically destroy sensory nerves to prevent the release of SP. After one week, full-thickness skin wounds were created on the rats′ back .SP content and EGF, EGFR, FGF-2, FGFR-1 gene expression in the granulation tissue were observed using immunohistochemistry and in situ hybridization combined with image analysis on 3 rd, 6 th, 9 th 12 th after skin injury, respectively . The experimental procedure in control group were similar with that in capsaicin group except injection with capsaicin. In vitro, SP (10 -9 -10 -5 mol/L) was added into culture medium for cultured fibroblasts from granulation and mRNA expressions of EGF, FGF-2 and their receptors were assayed with RT-PCR. Results In the present study, immunoreactive stain for SP in granulation tissue were correlated with gene expression of EGF,FGF-2 and their receptors using in situ hybridization in vivo. Once sensory nerves were destroyed and SP release was inhibited in capsaicin group, the gene expression of above growth factors and their receptors were attenuated. SP concentrations in culture medium for upregulation of mRNA expressions of EGF and EGFR in cultured fibroblasts were from 10 -8 mol/L to 10 -6 mol/L and from 10 -6 mol/L to 10 -5 mol/L, respectively. SP concentration was from 10 -9 mol/L to 10 -5 mol/L for upregulation of FGF-2 mRNA expression in cultured fibroblasts and from 10 -6 mol/L to 10 -5 mol/L for upregulation of FGFR-1. Conclusion Sensory neuropeptide SP released from sensory nerve participates in upregulation of gene expressions of EGF, EGF-2 and their receptors in granulation fibroblasts during wound healing.
出处 《中华医学杂志》 CAS CSCD 北大核心 2003年第16期1433-1436,共4页 National Medical Journal of China
基金 国家重点基础研究发展规划资助项目 (G19990 5 42 0 4)
关键词 感觉神经肽P物质 肉芽组织 成纤维细胞 表达 表皮生长因子 成纤维细胞生长因子-2 受体 调控 Substance P Epidermal growth factor Receptor,Epidermal growth factor Fibroblast growth factor
  • 相关文献

参考文献14

  • 1Schaffer M, Beiter T, Becker HD, et al. Neuropeptides:mediators of inflammation and tissue repair? Arch Surg,1998,133:1107-1116.
  • 2Nilsson J, Von Euler AM, Dalsgaard CJ. Stimulation of connective tissue cell growth by substance P and substance K. Nature,1985,315:61-63.
  • 3朱旭东 张艳 陈荣德 等.肉芽组织修复细胞的简易培养方法[J].中国修复重建外科杂志,1994,8:157-157.
  • 4Luger TA, Lotti T. Neuropeptides: role in inflammatory skin diseases. J Eur Acad Dermatol Venereol,1998,10: 207-211.
  • 5Braun S, auf dem Keller U, Beer HD,et al. Meeting report: growth factors in development, repair and disease. Eur J Cell Biol, 2002, 81: 375-382.
  • 6Song QH, Klepeis VE, Nugent MA,et al. TGF-betal regulates TGF-betal and FGF-2mRNA expression during fibroblast wound healing. Mol Pathol , 2002,55: 164-176.
  • 7Kayanoki Y, Higashiyama S, Suzuki K,et al. The requirement of both intracellular reactive oxygen species and intracellular calcium elevation for induction of heparin-binding EGF-like growth factor in vascular endothelial cells and smooth muscle cells. Biochem Biophys Res Commum, 1999,259:50-55.
  • 8Fiebich BL, Schleicher S, Butcher RD, et al. The neuropeptide substance P activates p38 mitogen-activated protein kinase resulting in IL-6 expression independently from NF-Kappa B. J Immunol,2000,165:5606-5611.
  • 9Ka minska B, Pyrzynska B, Ciechomska I, et al. Modulation of the composition of AP-1 complex and its impact on transcriptional activity. Acta Neurobiol Exp(Warsz),2000,60:395-402.
  • 10Christian C, Gilbert M, Payan DG. Stimulation of transcriptional regulatory activity by substance P. Neuroimmunomodulation,1996,1:159-164.

共引文献11

同被引文献128

引证文献10

二级引证文献83

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部