Disrupted local innervation results in less VIP expression in CF mice tissues

J Cyst Fibros. 2021 Jan;20(1):154-164. doi: 10.1016/j.jcf.2020.06.013. Epub 2020 Jun 27.

Abstract

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.

Keywords: Acetylcholine; Cystic fibrosis; Innervation; Intestine; Mice; VIP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cystic Fibrosis / metabolism*
  • Duodenum / innervation*
  • Duodenum / metabolism*
  • Lung / innervation*
  • Lung / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Sweat Glands / innervation*
  • Sweat Glands / metabolism*
  • Vasoactive Intestinal Peptide / biosynthesis*

Substances

  • Vasoactive Intestinal Peptide