Institute of Anatomy, Christian-Albrechts-University of Kiel, Kiel, Germany.
Department of Pathology, Städtisches Krankenhaus Kiel, Kiel, Germany.
United European Gastroenterol J. 2019 Apr;7(3):349-357. doi: 10.1177/2050640618824913. Epub 2019 Jan 16.
Diverticular disease, a major gastrointestinal disorder, is associated with modifications of the enteric nervous system, encompassing alterations of neurochemical coding and of the tyrosine receptor kinase Ret/GDNF pathway. However, molecular factors underlying these changes remain to be determined.
We aimed to characterise the expression of Phox2b, an essential regulator of Ret and of neuronal subtype development, in the adult human enteric nervous system, and to evaluate its potential involvement in acute diverticulitis.
Site-specific gene expression of Phox2b in the adult colon was analysed by quantitative polymerase chain reaction. Colonic specimens of adult controls and patients with diverticulitis were subjected to quantitative polymerase chain reaction for Phox2b and dual-label immunochemistry for Phox2b and the neuronal markers RET and tyrosine hydroxylase or the glial marker S100β.
The results indicate that Phox2b is physiologically expressed in myenteric neuronal and glial subpopulations in the adult enteric nervous system. Messenger RNA expression of Phox2b was increased in patients with diverticulitis and both neuronal, and glial protein expression of Phox2b were altered in these patients.
Alterations of Phox2b expression may contribute to the enteric neuropathy observed in diverticular disease. Future studies are required to characterise the functions of Phox2b in the adult enteric nervous system and to determine its potential as a therapeutic target in gastrointestinal disorders.
憩室病是一种主要的胃肠道疾病，与肠神经系统的改变有关，包括神经化学编码和酪氨酸受体激酶 Ret/GDNF 途径的改变。然而，这些变化背后的分子因素仍有待确定。
我们旨在研究 Phox2b 在成人肠神经系统中的表达特征，Phox2b 是 Ret 和神经元亚型发育的必需调节因子，并评估其在急性憩室炎中的潜在作用。
通过定量聚合酶链反应分析 Phox2b 在成人结肠中的特异性表达。对成人对照组和憩室炎患者的结肠标本进行 Phox2b 的定量聚合酶链反应和 Phox2b 与神经元标记物 RET 和酪氨酸羟化酶或神经胶质标记物 S100β 的双重免疫化学分析。
结果表明，Phox2b 在成人肠神经系统的肌间神经元和神经胶质亚群中具有生理表达。憩室炎患者的 Phox2b 信使 RNA 表达增加，这些患者的 Phox2b 神经元和神经胶质蛋白表达也发生改变。
Phox2b 表达的改变可能导致憩室病中观察到的肠神经病变。未来的研究需要阐明 Phox2b 在成人肠神经系统中的功能，并确定其作为胃肠道疾病治疗靶点的潜力。
