Grau Veronika, Wilker Sigrid, Hartmann Petra, Lips Katrin S, Grando Sergei A, Padberg Winfried, Fehrenbach Heinz, Kummer Wolfgang
Laboratory of Experimental Surgery, Department of General and Thoracic Surgery, University of Giessen Lung Center, Justus-Liebig-University Giessen, Rudolf Buchheim Str. 7, D-35385 Giessen, Germany.
Life Sci. 2007 May 30;80(24-25):2290-3. doi: 10.1016/j.lfs.2007.01.024. Epub 2007 Jan 23.
Administration of recombinant human keratinocyte growth factor (rHuKGF, Delta23N-KGF, palifermin) protects the lung against a variety of injurious stimuli. The exact mechanisms leading to lung protection are unknown. Alterations in the non-neuronal cholinergic system of the lung might be involved, as vital pulmonary functions are regulated by acetylcholine. Here, we investigated the effect of KGF on the expression of nicotinic acetylcholine receptor subunits alpha7, alpha9 and alpha10 in rat lungs. Adult rats were treated via intratracheal instillation with rHuKGF or with an equivalent volume of PBS. The expression of nicotinic acetylcholine receptor subunits was analyzed by real-time RT-PCR, immunoblotting and immunohistochemistry. Treatment with rHuKGF led to a decreased expression of nicotinic receptor subunit alpha7 in the total lung. In contrast, the expression of the receptor subunits alpha9 and alpha10 was up-regulated. In conclusion, nicotinic acetylcholine receptors are differentially regulated by KGF treatment in vivo, which might result in changes in the biological effects of acetylcholine.
重组人角质形成细胞生长因子(rHuKGF,Delta23N-KGF,帕利夫明)的给药可保护肺部免受多种损伤性刺激。导致肺部保护的确切机制尚不清楚。肺部非神经元胆碱能系统的改变可能与之有关,因为重要的肺功能受乙酰胆碱调节。在此,我们研究了KGF对大鼠肺中烟碱型乙酰胆碱受体亚基α7、α9和α10表达的影响。成年大鼠通过气管内滴注rHuKGF或等量的PBS进行处理。通过实时RT-PCR、免疫印迹和免疫组织化学分析烟碱型乙酰胆碱受体亚基的表达。用rHuKGF处理导致全肺中烟碱型受体亚基α7的表达降低。相反,受体亚基α9和α10的表达上调。总之,体内KGF处理对烟碱型乙酰胆碱受体有不同的调节作用,这可能导致乙酰胆碱生物学效应的改变。