Macrophage-mediated neuroprotection and neurogenesis in the olfactory epithelium
Macrophage-mediated neuroprotection and neurogenesis in the olfactory epithelium
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DOI：
10.1152/physiolgenomics.00008.2007
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发表时间：
2007-11-14
影响因子：
4.6
通讯作者：
Getchell, T. V.
中科院分区：
文献类型：
--
作者：
Borders, A. S.;Hersh, M. A.;Getchell, T. V.
常驻和招募的嗅上皮巨噬细胞参与嗅觉感觉神经元（OSN）的存活、变性和替换的调节。我们报道，与对照（Lip-O）相比，脂质体封装的氯膦酸盐（Lip-C）诱导假手术小鼠和48小时OBX小鼠（分别为38％和35％）的OE中巨噬细胞的选择性和统计显着性消耗，导致OSN凋亡增加，成熟OSN和增殖基底细胞的数量减少。本研究的目的是通过使用微阵列表达模式分析来确定 OE 中巨噬细胞的选择性耗竭导致这些细胞变化的分子机制。 2 x 2 方差分析在 Lip-O 和 Lip-C 假小鼠和 48 小时 OBX 小鼠的 OE 中鉴定出 4,085 个总体显着（P < 0.01）调节的基因，并使用成对比较进行进一步统计分析，鉴定了 4,024 个基因，这些基因具有显着（P < 0.01）治疗主效应（n = 2,680）、组主效应（n = 778）或相互作用效应（n = 980）。免疫反应基因的平均杂交信号，例如。例如，Cxcr4，以及编码生长因子和神经发生调节剂的基因，例如与 Lip-O 小鼠相比，Lip-C 小鼠中的 g.、Hdgf 和 Neurod1 分别主要较低。凋亡基因，e．例如，Bak1，在 Lip-C 和/或 OBX 小鼠中也受到差异调节。通过实时 RT-PCR 验证所选基因的表达模式；免疫组织化学用于定位选定的基因产物。这些结果确定了几个新基因的差异调节，交替激活的巨噬细胞通过这些基因调节 OSN 祖细胞增殖、分化和成熟以及 OSN 的存活。
Resident and recruited olfactory epithelial macrophages participate in the regulation of the survival, degeneration, and replacement of olfactory sensory neurons (OSNs). We have reported that liposome-encapsulated clodronate (Lip-C) induced selective and statistically significant depletion of macrophages in the OE of sham and 48 h OBX mice (38 and 35%, respectively) that resulted in increased OSN apoptosis and decreased numbers of mature OSNs and proliferating basal cells compared to controls (Lip-O). The aim of this study was to identify molecular mechanisms by which the selective depletion of macrophages in the OE resulted in these cellular changes by using a microarray expression pattern analysis. A 2 x 2 ANOVA identified 4,085 overall significantly (P < 0.01) regulated genes in the OE of Lip-O and Lip-C sham and 48 h OBX mice, and further statistical analysis using pairwise comparisons identified 4,024 genes that had either a significant (P < 0.01) treatment main effect (n = 2,680), group main effect (n = 778), or interaction effect (n = 980). The mean hybridization signals of immune response genes, e. g., Cxcr4, and genes encoding growth factors and neurogenesis regulators, e. g., Hdgf and Neurod1, respectively, were primarily lower in Lip-C mice compared with Lip-O mice. Apoptosis genes, e. g., Bak1, were also differentially regulated in Lip-C and/or OBX mice. Expression patterns of selected genes were validated with real-time RT-PCR; immunohistochemistry was used to localize selected gene products. These results identified the differential regulation of several novel genes through which alternatively activated macrophages regulate OSN progenitor cell proliferation, differentiation, and maturation, and the survival of OSNs.