FIZZ1, a novel cysteine-rich secreted protein associated with pulmonary inflammation, defines a new gene family

FIZZ1, a novel cysteine-rich secreted protein associated with pulmonary inflammation, defines a new gene family
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DOI:
10.1093/emboj/19.15.4046
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发表时间:
2000-08-01
期刊:
影响因子:
11.4
通讯作者:
Hébert, CC
Hébert, CC
中科院分区:
生物学1区
文献类型:
--
作者:
Holcomb, IN;Kabakoff, RC;Hébert, CC

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实验诱导的过敏性肺部炎症小鼠的支气管肺泡灌洗液含有一种新的9.4 kDa富含半胱氨酸的分泌蛋白FIZZ1(在炎症区发现)。小鼠(m) FIZZ1是一个新基因家族的创始成员,该家族包括另外两个分别在肠隐窝上皮和白色脂肪组织中表达的小鼠基因,以及两个相关的人类基因。在对照小鼠中,FIZZ1 mRNA和蛋白在支气管上皮细胞亚群、支气管周围基质中神经维管束附近的非神经元细胞以及大肠壁和小肠壁中低水平表达。在变应性肺部炎症期间,mFIZZ1在增生性支气管上皮和II型肺泡肺细胞中表达显著增加。在体外,重组mFIZZ1抑制神经生长因子(NGF)介导的大鼠胚胎第14天背根神经节(DRG)神经元的存活和NGF诱导的成年大鼠DRG神经元CGRP基因的表达。在体内,FIZZ1可能调节支配支气管树的神经元的功能,从而改变局部组织对过敏性肺部炎症的反应。
Bronchoalveolar lavage fluid from mice with experimentally induced allergic pulmonary inflammation contains a novel 9.4 kDa cysteine-rich secreted protein, FIZZ1 (found in inflammatory zone). Murine (m) FIZZ1 is the founding member of a new gene family including two other murine genes expressed, respectively, in intestinal crypt epithelium and white adipose tissue, and two related human genes. In control mice, FIZZ1 mRNA and protein expression occur at low levels in a subset of bronchial epithelial cells and in non-neuronal cells adjacent to neurovascular bundles in the peribronchial stroma, and in the wall of the large and small bowel. During allergic pulmonary inflammation, mFIZZ1 expression markedly increases in hypertrophic, hyperplastic bronchial epithelium and appears in type II alveolar pneumocytes. In vitro, recombinant mFIZZ1 inhibits the nerve growth factor (NGF)-mediated survival of rat embryonic day 14 dorsal root ganglion (DRG) neurons and NGF-induced CGRP gene expression in adult rat DRG neurons. lit vivo, FIZZ1 may modulate the function of neurons innervating the bronchial tree, thereby altering the local tissue response to allergic pulmonary inflammation.