Roles of Calcitonin Gene–Related Peptide in Maintenance of Gastric Mucosal Integrity and in Enhancement of Ulcer Healing and Angiogenesis

Gong²,

J Neurogastroenterol Motil

et al. 2015

Background/Aims There are increasing evidences for gastrointestinal motility disorder (GIMD) and gastric stress ulcer induced by noise stress. The present study was to investigate the reversed effect of melatonin on GIMD and gastric stress ulcer induced by noise stress and potential mechanism. Methods Noise stress was induced on rats, and melatonin (15 mg/kg) was administered to rats by intraperitoneal injection. Differences were assessed in gastric residual rate (GRR), small intestine propulsion rate (SPR), Guth injury score, cortisol, gastrointestinal hormones (calcitonin-gene-related peptide and motilin) and oxidative stress markers (superoxide dismutase and malondialde hyde) in blood plasma as well as gastric mucosa homogenate with or without melatonin. The pathological examination of gastric mucosa was also performed. Results The GRR and SPR were improved by noise stress compared with control ( P < 0.05). The pathological examination and Guth injury score revealed gastric stress ulcer. Moreover, the levels of cortisol, motilin and malondialdehyde in blood plasma and malondialdehyde in gastric mucosa homogenate were increased by noise stress ( P < 0.05). CGRP and superoxide dismutase activity in both of blood plasma and gastric mucosa homogenate were significantly decreased ( P < 0.05). Furthermore, melatonin reversed changes in GRR, SPR, pathological examination, Guth injury score, cortisol, motilin, CGRP, superoxide dismutase activity and malondialdehyde ( P < 0.05). Conclusions Melatonin is effective in reversing the GIMD and gastric stress ulcer induced by noise stress. The underlying mechanism may be involved in oxidative stress and gastrointestinal hormones.

Section: Discussionmentioning

confidence: 99%

“…60 Exogenous CGRP shows protective effect to reflux esophagitis 61 and gastric mucosa ulcer. 48,49 However, it is reported that GIMD is observed in patients with ulcers and those with non-ulcer dyspepsia compared with asymptomatic controls. 62 That may indicate that gastric ulcer may influent GI motility itself.…”

Section: +mentioning

confidence: 99%

Melatonin Attenuates Noise Stress-induced Gastrointestinal Motility Disorder and Gastric Stress Ulcer: Role of Gastrointestinal Hormones and Oxidative Stress in Rats

Gong²,

J Neurogastroenterol Motil

et al. 2015

“…In the sponge model, granulation tissues with the property of chronic inflammation were formed around the sponge implants with enough reproducibility, and we can easily determine the active molecules at the site of the chronic inflammation, because rapid sampling and easy extractions of active molecules and mRNA can be performed in the sponge model. The results with this sponge model have been published in some journals, 5,6,26,27,29,[31][32][33][34][35][36][37][38][39][40] and many researchers have a strong interest in this model. In the beginning of this study, we had tried to test this sponge model to clarify the involvement of PGs in lymphangiogenesis during the chronic inflammation, but the detection of newly developed lymphatics was quite difficult in the sponge model.…”

Section: Discussionmentioning

confidence: 99%

Roles of Prostaglandin E ₂ –EP3/EP4 Receptor Signaling in the Enhancement of Lymphangiogenesis During Fibroblast Growth Factor-2–Induced Granulation Formation

Hosono

Suzuki

Tamaki

et al. 2011

ATVB

Self Cite

Objective— One of the hallmarks of inflammation is lymphangiogesis that drains the interstitial fluids. During chronic inflammation, angiogenesis is induced by a variety of inflammatory mediators, such as prostaglandins (PGs). However, it remains unknown whether they enhance lymphangiogenesis. We examined the roles of cyclooxygenase-2 (COX-2) and PGE 2 receptor signaling in enhancement of lymphangiogenesis during proliferative inflammation. Methods and Results— Lymphangiogenesis estimated by podoplanin/vascular endothelial growth factor (VEGF) receptor-3/LYVE-1 expression was upregulated during proliferative inflammation seen around and into subcutaneous Matrigel plugs containing fibroblast growth factor-2 (125 ng/site). A COX-2 inhibitor (celecoxib) significantly reduced lymphangiogenesis in a dose-dependent manner, whereas topical PGE 2 enhanced lymphangiogenesis. Topical injection of fluorescein isothiocyanate–dextran into the Matrigel revealed that lymphatic flow from the Matrigels was COX-2 dependent. Lymphangiogenesis was suppressed in the granulation tissues of mice lacking either EP3 or EP4, suggesting that these molecules are receptors in response to endogenous PGE 2 . An EP3-selective agonist (ONO-AE-248) increased the expression of VEGF-C and VEGF-D in cultured macrophages, whereas an EP4-selective agonist (ONO-AE1-329) increased VEGF-C expression in cultured macrophages and increased VEGF-D expression in cultured fibroblasts. Conclusion— Our findings suggest that COX-2 and EP3/EP4 signaling contributes to lymphangiogenesis in proliferative inflammation, possibly via induction of VEGF-C and VEGF-D, and may become a therapeutic target for controlling lymphangiogenesis.

“…Inada et al [4] reported that LPZ increased basic and acid-induced bicarbonate secretion by stimulating capsaicin-sensitive sensory neurons, but neither famotidine nor omeprazole could bring about that effect. Ohno et al [32] reported that, compared to wild-type (WT) mice, calcitonin gene-related peptide (CGRP) knockout mice showed a delay in acid-induced ulcer healing and a reduction in ulcer granulation and VEGF-A expression. They also discussed that CGRF with PGs derived from COX-2 enhanced angiogenesis and ulcer healing via the upregulation of VEGF.…”

Section: Discussionmentioning

confidence: 99%

Effects of lansoprazole on the expression of VEGF and cellular proliferation in a rat model of acetic acid-induced gastric ulcer

et al. 2010

One of the mechanisms of ulcer healing brought about by LPZ may be the involvement of endogenous prostaglandin (PG) secretion. The effect of endogenous PG secretion may be related to the induction of VEGF expression. On the other hand, LPZ administration increased MMP-2 expression, and this effect was not influenced by the inhibition of PG synthesis. The mechanisms of LPZ on ulcer healing may be involved by VEGF expression through endogenous PGs secretion. Additionally, the stimulated expression of MMP-2, which is not secreted by endogenous PGs, is another important factor for ulcer healing by LPZ.