Expression and function of Neuregulin 1 and its signaling system ERBB2/3 in the enteric nervous system.
Expression and function of Neuregulin 1 and its signaling system ERBB2/3 in the enteric nervous system.
复制标题
DOI：
10.3389/fncel.2015.00360
复制
发表时间：
2015
影响因子：
5.3
通讯作者：
Böttner M
中科院分区：
文献类型：
--
作者：
Barrenschee M;Lange C;Cossais F;Egberts JH;Becker T;Wedel T;Böttner M
神经调节蛋白1（NRG 1）被认为促进肠神经系统（ENS）的存活和维持。由于其相应的受体信号复合物ERBB 2/ERBB 3的缺陷导致出生后结肠神经节细胞减少/无神经节细胞增多症，我们评估了NRG 1-ERBB 2/ERBB 3系统在人结肠中的分布和表达模式，并探索了NRG 1对培养的肠神经元的神经营养能力。在从肠肌肉组织和神经节收获的显微解剖样品中确定NRG 1-ERBB 2/3系统的位点特异性mRNA表达。使用泛神经元和泛神经胶质标记物通过双标记免疫组织化学确定NRG 1、ERBB 2和ERBB 3的定位。对NRG 1刺激的大鼠肠神经培养物进行形态测定分析以评价神经营养作用。通过qPCR测定NRG 1-ERBB 2/3系统的mRNA表达。在用胶质细胞源性神经营养因子（GDNF）刺激的肠神经培养物中分析了NRG 1与神经元或突触标记物的共定位。NRG 1系统在肠神经节的神经元和胶质细胞以及神经纤维中均有表达。NRG 1显着增强肠神经细胞培养的生长参数和ErB 3 mRNA表达下调后NRG 1刺激。GDNF负调控ErbB 2和ErbB 3 mRNA的表达。NRG 1-ERBB 2/3系统在生理上存在于人ENS中，并且NRG 1充当ENS的神经营养因子。在GDNF刺激的神经细胞培养物中ErbB 3/ErbB 2的下调指出两种神经营养因子的相互作用。因此，这些数据可以提供一个基础，以评估肠神经病变的NRG 1系统的干扰信号成分。
Neuregulin 1 (NRG1) is suggested to promote the survival and maintenance of the enteric nervous system (ENS). As deficiency in its corresponding receptor signaling complex ERBB2/ERBB3 leads to postnatal colonic hypo/aganglionosis we assessed the distributional and expressional pattern of the NRG1-ERBB2/ERBB3 system in the human colon and explored the neurotrophic capacity of NRG1 on cultured enteric neurons. Site-specific mRNA expression of the NRG1-ERBB2/3 system was determined in microdissected samples harvested from enteric musculature and ganglia. Localization of NRG1, ERBB2 and ERBB3 was determined by dual-label-immunohistochemistry using pan-neuronal and pan-glial markers. Morphometric analysis was performed on NRG1-stimulated rat enteric nerve cultures to evaluate neurotrophic effects. mRNA expression of the NRG1-ERBB2/3 system was determined by qPCR. Co-localization of NRG1 with neuronal or synaptic markers was analyzed in enteric nerve cultures stimulated with glial cell line-derived neurotrophic factor (GDNF). The NRG1 system was expressed in both neurons and glial cells of enteric ganglia and in nerve fibers. NRG1 significantly enhanced growth parameters in enteric nerve cell cultures and ErB3 mRNA expression was down-regulated upon NRG1 stimulation. GDNF negatively regulates ErbB2 and ErbB3 mRNA expression. The NRG1-ERBB2/3 system is physiologically present in the human ENS and NRG1 acts as a neurotrophic factor for the ENS. The down-regulation of ErbB3/ErbB2 in GDNF stimulated nerve cell cultures points to an interaction of both neurotrophic factors. Thus, the data may provide a basis to assess disturbed signaling components of the NRG1 system in enteric neuropathies.