Vasoactive Intestinal Peptide (VIP) is the major physiological agonist of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) chloride channel activity. VIP functions as a neuromodulator and neurotransmitter secreted by neurons innervating all exocrine glands. VIP is also a potent vasodilator and bronchodilator that regulates exocrine gland secretions, contributing to local innate defense by stimulating the movement of water and chloride transport across intestinal and tracheobronchial epithelia. Previous human studies have shown that the rich intrinsic neuronal networks for VIP secretion around exocrine glands could be lost in tissues from patients with cystic fibrosis. Our research has since confirmed, in vitro and in vivo, the need for chronic VIP exposure to maintain functional CFTR chloride channels at the cell surface of airways and intestinal epithelium, as well as normal exocrine tissues morphology [1]. The goal of the present study was to examine changes in VIP in the lung, duodenum and sweat glands of 8- and 17-weeks old F508del/F508del mice and to investigate VIPergic innervation in the small intestine of CF mice, before important signs of the disease development. Our data show that a low amount of VIP is found in CF tissues prior to tissue damage. Moreover, we found a specific reduction in VIPergic and cholinergic innervation of the small intestine. The general innervation of the primary and secondary myenteric plexus was lost in CF tissues, with the presence of enlarged ganglionic cells in the tertiary layer. We propose that low amount of VIP in CF tissues is due to a reduction in VIPergic and cholinergic innervation and represents an early defect that constitutes an aggravating factor for CF disease progression.

中文翻译：

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局部神经支配中断导致 CF 小鼠组织中 VIP 表达减少

血管活性肠肽 (VIP) 是囊性纤维化跨膜电导调节剂 (CFTR) 氯通道活性的主要生理激动剂。VIP 充当神经调节剂和神经递质，由支配所有外分泌腺的神经元分泌。VIP 还是一种有效的血管扩张剂和支气管扩张剂，可调节外分泌腺分泌物，通过刺激水和氯离子转运穿过肠道和气管支气管上皮的运动，促进局部先天防御。先前的人类研究表明，囊性纤维化患者的组织中可能会丢失用于外分泌腺周围 VIP 分泌的丰富的内在神经元网络。我们的研究已经在体外和体内证实，需要长期暴露于 VIP 以维持气道和肠上皮细胞表面的功能性 CFTR 氯离子通道，以及正常的外分泌组织形态 [1]。本研究的目的是检查 8 周龄和 17 周龄 F508del/F508del 小鼠肺、十二指肠和汗腺中 VIP 的变化，并研究 CF 小鼠小肠中 VIPergic 神经支配的重要迹象之前疾病发展。我们的数据显示，在组织损伤之前，在 CF 组织中发现了少量的 VIP。此外，我们发现小肠 VIPergic 和胆碱能神经支配的特定减少。初级和次级肌间神经丛的一般神经支配在 CF 组织中丢失，第三层中存在增大的神经节细胞。