Butyrate promotes visceral hypersensitivity in an IBS-like model via enteric glial cell-derived nerve growth factor
Butyrate promotes visceral hypersensitivity in an IBS-like model via enteric glial cell-derived nerve growth factor
复制标题
丁酸盐通过肠胶质细胞衍生的神经生长因子促进 IBS 样模型中的内脏过敏。
DOI：
10.1111/nmo.13227
复制
发表时间：
2018-04-01
影响因子：
3.5
通讯作者：
Li, Y. -Q.
中科院分区：
文献类型：
--
作者：
Long, X.;Li, M.;Li, Y. -Q.
肠易激综合征(IBS)常见内脏感觉改变，神经生长因子(NGF)参与内脏疼痛的发生发展。丁酸钠(NAB)可通过上调周围神经生长因子(NGF)诱导动物结肠超敏反应。肠胶质细胞(EGCs)似乎是NGF的重要来源。丁酸是否通过增加EGC来源的NGF诱导内脏高敏感性尚不清楚。方法用丁酸处理CRL-2690细胞进行转录组分析。大鼠接受丁酸盐灌肠诱导结肠过敏反应。进行结肠扩张试验以评估内脏敏感性。用免疫荧光方法检测胶质纤维酸性蛋白(GFAP)和神经生长因子(NGF)或生长相关蛋白43在动物模型中的共表达。同时观察NGF在大鼠结肠中的表达。在体外，用NAB或曲古抑素A(TSA)刺激CRL-2690细胞。关键结果转录组分析显示，丁酸诱导神经营养信号通路相关基因的表达发生明显变化。NAB处理的大鼠表现出内脏敏感性增加。在NAB处理的大鼠中观察到NGF表达水平的提高。同时，在接受NAB灌肠的大鼠中，GFAP和NGF的共同表达也增加了2.1倍。在培养细胞中，NAB和TSA处理均可引起明显的NGF表达。结论丁酸-EGC相互作用可能在IBS样动物模型中NGF的表达调控和结肠超敏反应的发生发展中起关键作用。
BackgroundAltered visceral sensation is common in irritable bowel syndrome (IBS) and nerve growth factor (NGF) participates in visceral pain development. Sodium butyrate (NaB) could induce colonic hypersensitivity via peripheral up-regulation of NGF in animals. Enteric glial cells (EGCs) appear to be an important source of NGF. Whether butyrate could induce visceral hypersensitivity via increased EGC-derived NGF is still unknown.MethodsCRL-2690 cells were used for transcriptome analyses after butyrate treatment. Rats received butyrate enemas to induce colonic hypersensitivity. Colorectal distention test was performed to assess visceral sensitivity. Immunofluorescence studies were used to evaluate the co-expression of glial fibrillary acidic protein (GFAP) and NGF or growth associated protein 43 in animal model. NGF expression in rat colon was also investigated. In vitro, CRL-2690 cells were stimulated with NaB or trichostatin A (TSA). NGF or GFAP expression was also examined.Key ResultsTranscriptome analyses showed that butyrate induced marked changes of genes expression related to neurotrophic signaling pathways. NaB-treated rats showed increased visceral sensitivity. An improved NGF expression level was observed in NaB-treated rats. Meanwhile, a 2.1-fold increase in co-expression of GFAP and NGF was also determined in rats received NaB enemas. In cultured cells, both NaB and TSA treatment could cause obvious NGF expression. Thus, butyrate might regulate EGC function via histone deacetylase inhibition.Conclusions & InferencesButyrate-EGC interplay may play a pivotal role in regulation of NGF expression and the development of colonic hypersensitivity in IBS-like animal model.