Role of microsomal prostaglandin E synthase-1 in the facilitation of angiogenesis and the healing of gastric ulcers

Abstract

The importance of prostaglandin E(2) in various pathophysiological events emphasizes the necessity of understanding the role of PGE synthases (PGESs) in vivo. However, there has been no report on the functional relevance of microsomal PGES-1 (mPGES-1) to the physiological healing processes of gastric ulcers, or to angiogenesis, which is indispensable to the healing processes. In this report, we tested whether mPGES-1 plays a role in the healing of gastric ulcers and in the enhancement of angiogenesis using mPGES-1 knockout mice (mPGES-1 KO mice) and their wild-type (WT) counterparts. Gastric ulcers were induced by the serosal application of 100% acetic acid, and the areas of the ulcers were measured thereafter. mPGES-1 together with cyclooxygenase-2 were induced in the granulation tissues compared with normal stomach tissues. The healing of acetic acid-induced ulcers was significantly delayed in mPGES-1 KO mice compared with WT. This was accompanied with reduced angiogenesis in ulcer granulation tissues, as estimated by CD31 mRNA levels determined by real-time PCR and the microvessel density in granulation tissues. The mRNA levels of proangiogenic growth factors, such as transforming growth factor-β, basic fibroblast growth factor, and connective tissue growth factor in ulcer granulation tissues determined were reduced in mPGES-1 KO mice compared with WT. The present results suggest that mPGES-1 enhances the ulcer-healing processes and the angiogenesis indispensable to ulcer healing, and that a selective mPGES-1 inhibitor should be used with care in patients with gastric ulcers.

Effect of local injection of mesenchymal stem cells on healing of sutured gastric perforation in an experimental model

“…VEGF and COX‐2 have been suggested to be upregulated during gastric ulcer healing, and mesenchymal stem cells are believed to promote vascularization. Here, local transplantation of mesenchymal stem cells did not affect angiogenesis in granulation tissue of the gastric wound, as there were no differences between the four experimental groups on day 7 in blood vessel density, indicated by CD31 staining, and expression levels of VEGF and COX‐2 were not significantly different between the groups on day 7 ( Fig.…”

Adenosine A2A-receptor agonist polydeoxyribonucleotide promotes gastric ulcer healing in Mongolian gerbils

“…Reduced angiogenesis disturbed the healing process in acetic acid-induced GU (Ae et al 2010). VEGF was detected in the margins of human GU and was released from gastric fibroblasts (Ae et al 2010;Sato et al 2013). Here, PDRN administration enhanced VEGF expression in the GU region.…”

“…PDRN stimulated fibroblast maturation and enhanced VEGF production in the incision skin wound (Bitto et al 2008). Reduced angiogenesis disturbed the healing process in acetic acid-induced GU (Ae et al 2010). VEGF was detected in the margins of human GU and was released from gastric fibroblasts (Ae et al 2010;Sato et al 2013).…”

Multifaceted roles of PGE2 in inflammation and cancer

“…As noted by Allen et al [45], T H 2-type cytokines have been postulated to promote localized wound healing by enhancing M2-type macrophage activity that facilitates the production of proteins associated with accelerated tissue repair. The direct involvement of PGE 2 in wound healing has been demonstrated by Ae et al [46], where mPGES-1 deficient mice exhibit delayed healing following acetic acid-induced gastric ulceration. Furthermore, the absence of inducible mPGES-1 caused an enhanced sensitivity to dextran sodium sulfate (DSS) treatment, with the development of a more severe ulcerative colitis phenotype in the KOs compared to wild-type mice [25].…”