Vasoactive Intestinal Polypeptide Promotes Intestinal Barrier Homeostasis and Protection Against Colitis in Mice

Wu, Xiujuan; Conlin, Victoria S.; Morampudi, Vijay; Ryz, Natasha R.; Nasser, Yasmin; Bhinder, Ganive; Bergstrom, Kirk; Yu, Hong; Waterhouse, Chris C. M.; Buchan, A.M.J.; Popescu, Oana; Gibson, William T.; Waschek, James A.; Vallance, Bruce A.; Jacobson, Kevan

doi:10.1371/journal.pone.0125225

Cited by 47 publications

(68 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In Vip KO mice, there is less production of goblet cells and low secretion of Tff3/Muc2, whereas colonic mucosal permeability and susceptibility to dinitrobenzene sulfonic acid-induced damage are increased. These effects can be reversed by stimulation of Tff3/Muc2 production following VIP administration, implicating TFF3 in intestinal barrier protection (38). …”

Section: Trefoil Factor Peptides Enhance Gastrointestinal Mucosal Defmentioning

confidence: 99%

“…Tff3 is also increased in response to DSS-induced colitis in mice, however, there was no detection of Tff1 and Tff2 (137). Regeneration of colonic epithelium following injury was impaired in Tff3 KO or Vip KO (with less Tff3/Muc2) mice (32, 38). Colonic luminal application of recombinant TFF3 improved mucosal healing of acetic acid-induced injury in Tff3 KO mice (32) and after ischemia-reperfusion-induced injury in rats (52).…”

Section: Trefoil Factor and Gastrointestinal Diseasesmentioning

confidence: 99%

“…Recently, a decreased number of periodic acid-schiff positive goblet cells, accompanied with reduction of Tff3 and Muc2 expression, was observed in vasoactive intestinal polypeptide (Vip, a peptide hormone) KO mice, and exogenous administration of recombinant VIP increased Tff3/Muc2 production by the goblet cells (38). This provides the first evidence that TFF3 production is regulated by hormones and that the beneficial effects of VIP may in part be mediated by TFF3.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Trefoil Factor Peptides and Gastrointestinal Function

Aihara

Engevik²,

Montrose³

2017

Annu. Rev. Physiol.

150

123

View full text Add to dashboard Cite

Trefoil factor (TFF) peptides, containing a 40-amino acid motif, including six conserved cysteine residues that form intramolecular disulfide bonds, are a family of mucin-associated secretory molecules mediating many physiological roles that maintain and restore gastrointestinal (GI) mucosal homeostasis. TFF peptides play important roles in response to GI mucosal injury and inflammation. In response to acute GI mucosal injury, TFF peptides accelerate cell migration to seal the damaged area from luminal contents, whereas chronic inflammation leads to increased TFF expression to prevent further progression of disease. Although much evidence supports the physiological significance of TFF peptides in mucosal defenses, the molecular and cellular mechanisms of TFF peptides in the GI epithelium remain largely unknown. In this review, we summarize the functional roles of TFF1, 2, and 3 and illustrate their action mechanisms, focusing on defense mechanisms in the GI tract.

show abstract

Section: Trefoil Factor Peptides Enhance Gastrointestinal Mucosal Defmentioning

confidence: 99%

Section: Trefoil Factor and Gastrointestinal Diseasesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Trefoil Factor Peptides and Gastrointestinal Function

Aihara

Engevik²,

Montrose³

2017

Annu. Rev. Physiol.

150

123

View full text Add to dashboard Cite

show abstract

“…4,9,13–16 However, the therapeutic role of VIP in managing UC is still not well established and conflicting findings have been reported. 17,18 The labile peptide VIP undergoes rapid degradation once administered systemically; therefore, delivering the required amounts of the peptide to the target site becomes challenging. 19 In order to be effective in vivo, the free VIP needs to be administered parenterally at higher doses and with increased frequency, which results in severe toxicities such as hypotension and tachycardia.…”

Section: Introductionmentioning

confidence: 99%

Vasoactive Intestinal Peptide Nanomedicine for the Management of Inflammatory Bowel Disease

Jayawardena¹,

Anbazhagan²,

Guzman³

et al. 2017

Mol. Pharmaceutics

View full text Add to dashboard Cite

Inflammatory bowel disease (IBD) is a chronic relapsing disorder of the intestine, with increasing incidence worldwide. At present, the management of IBD is an unmet medical need due to the ineffectiveness of currently available drugs in treating all patients, and there is strong demand for novel therapeutics. In this regard, vasoactive intestinal peptide, a potent anti-inflammatory endogenous hormone, has shown promise in managing multiple immune disorders in animal models. However, when administered in the free form, VIP undergoes rapid degradation in vivo, and with continuous infusion, it causes severe dose limiting side effects. To overcome these barriers, we have developed a superior mode to deliver VIP in its native form, using sterically stabilized micelles (VIP-SSM). Our previous studies demonstrated that, VIP, when administered in SSM, prevented joint damage and inflammation in a mouse model of rheumatoid arthritis at a significantly lower dose than the free peptide, completely abrogating the serious side effect of hypotension associated with VIP. In the current study, we demonstrate the therapeutic benefit of VIP-SSM over free peptide in reversing severe colitis associated with IBD. First, we conducted preliminary studies with dextran sulfate sodium (DSS) induced colitis in mice, to determine the effectiveness of VIP administered on alternate days in reducing disease severity. Thereafter, a single intra peritoneal injection of VIP-SSM or the free peptide was used to determine its therapeutic effect on the reversal of colitis and associated diarrhea. The results demonstrated that when administered on alternate days, both VIP-SSM and VIP were capable of alleviating DSS colitis in mice. However, when administered as a single dose, in a therapeutic setting, VIP-SSM showed superior benefits compared to the free peptide in ameliorating colitis phenotype. Namely, the loss of solid fecal pellets and increased fluid accumulation in colon resulting from DSS insult was abrogated in VIP-SSM treated mice and not with free VIP. Furthermore, reduced protein and mRNA levels of the major chloride bicarbonate exchanger, down regulated in adenoma (DRA), seen with DSS was reversed with VIP-SSM, but not with the free peptide. Similarly, VIP-SSM treatment significantly reduced the elevated mRNA levels of pro-inflammatory cytokines and showed significant histologic recovery when compared to mice treated with free VIP. Therefore, these results demonstrated that as a single dose, the anti-inflammatory and antidiarrheal effects of VIP can be achieved effectively when administered as a nanomedicine. Therefore, we propose VIP-SSM to be developed as a potential therapeutic tool for treating ulcerative colitis, a type of IBD.

show abstract

“…Finally, in 2015 Wu et al evaluated a VIP knockout animal using dinitrobenzene sulfonic acid (DNBS) or DSS treatments and found that they developed more severe colitis. In an elegant study, the knockout animals were treated with exogenous VIP, which rescued the phenotype [65]. Overall, these seemingly controversial results highlight the complexity of VIP signaling and the context dependent signaling that is at play in each of these models.…”

Section: Vasoactive Intestinal Polypeptide (Vip) and Colitismentioning

confidence: 99%