Role of growth factors in the repair of gastric mucosal injury

The major objective of this study was to elucidate the role of endogenous endothelin (ET)-1, a potent vasoconstrictor peptide, in the pathogenesis of ethanol (EtOH)-induced gastric mucosal injury. Two series of experiments were performed in anesthetized rats. First, we examined the time course of relationships among changes in ET-1 concentrations in gastric mucosal and portal plasma, gastric mucosal hemodynamics, and mucosal damage produced by EtOH. Intragastric EtOH stimulated release of endogenous ET-1 in gastric mucosal tissue. Plasma ET-1 concentrations in the portal vein also increased after intragastric EtOH administration. ET-1 concentrations in gastric mucosal tissue and portal plasma increased significantly before gastric mucosal hemorrhagic damage occurred. Moreover, 30 min after EtOH administration there were significant correlations between gastric mucosal ET-1 concentrations and both area of gastric hemorrhagic damage as well as concentration of EtOH administered intragastrically. After intragastric EtOH administration, increase in gastric mucosal hemoglobin concentration and decrease in gastric mucosal hemoglobin oxygen saturation, estimated using reflectance spectrophotometry, occurred within 2.5 min and continued throughout the experiments. The time course of microcirculatory changes correlated closely with increases in gastric mucosal ET-1 and portal plasma ET-1 concentrations after intragastric EtOH administration. Gastric microcirculatory disturbances induced by EtOH were associated with significant decreases in gastric mucosal ATP content. Second, we examined whether pretreatment with anti-ET-1 antibody protected against EtOH-induced mucosal injury by improving mucosal microcirculation. Pretreatment with anti-ET-1 antibody microscopically and macroscopically reduced gastric mucosal hemorrhagic damage induced by EtOH and significantly reduced EtOH-induced gastric microcirculatory disturbances and decreases in gastric mucosal ATP.(ABSTRACT TRUNCATED AT 250 WORDS)

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Role of endothelin 1 in hemorrhagic shock-induced gastric mucosal injury in rats

Gastroenterology ◽

10.1016/0016-5085(94)90758-7 ◽

1994 ◽

Vol 106 (4) ◽

pp. 988-993 ◽

Cited By ~ 50

Author(s):

Tomoki Michida ◽

Sunao Kawano ◽

Eiji Masuda ◽

Ichizo Kobayashi ◽

Yoshiya Nishimura ◽

...

Keyword(s):

Hemorrhagic Shock ◽

Mucosal Injury ◽

Gastric Mucosal Injury ◽

Endothelin 1

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The Role of Motility in Gastric Mucosal Injury and Protection

Drug Investigation ◽

10.1007/bf03259176 ◽

1990 ◽

Vol 2 (S1) ◽

pp. 31-31

Author(s):

J.E. Valenzuela

Keyword(s):

Mucosal Injury ◽

Gastric Mucosal Injury

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Protective role of adiponectin against ethanol-induced gastric injury in mice

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00324.2011 ◽

2012 ◽

Vol 302 (8) ◽

pp. G773-G780 ◽

Cited By ~ 15

Author(s):

Shunsuke Yamamoto ◽

Kenji Watabe ◽

Hiroshi Araki ◽

Yoshihiro Kamada ◽

Motohiko Kato ◽

...

Keyword(s):

Wound Repair ◽

Mucosal Injury ◽

Protective Role ◽

Gastric Mucosal Injury ◽

Serum Adiponectin ◽

Gastric Injury ◽

Prostaglandin E ◽

Ethanol Treatment ◽

Cox 2

Adiponectin is an anti-inflammatory molecule released from adipocytes, and serum adiponectin concentrations are reduced in obesity. We previously reported that gastric erosion occurs in association with obesity and low serum adiponectin levels. In the present study, we examined adiponectin-knockout (APN-KO) mice to elucidate the role of adiponectin in gastric mucosal injury. Gastric injury was induced by oral administration of ethanol in wild-type (WT) and APN-KO mice. Ethanol treatment induced severe gastric injury in APN-KO mice compared with WT mice. In APN-KO mice, increased apoptotic cells and decreased expression of prostaglandin E2 (PGE2) were detected in the injured stomach. We next assessed the effect of adiponectin on the cellular response to ethanol treatment and wound repair in rat gastric mucosal cells (RGM1). Adiponectin induced the expression of PGE2 and cyclooxygenase 2 (COX-2) in ethanol-treated RGM1 cells. RGM1 cells exhibited efficient wound repair accompanied by increased PGE2 expression in the presence of adiponectin. Coadministration of adiponectin with celecoxib, a COX-2 inhibitor, inhibited efficient wound repair. These findings indicate that adiponectin has a protective role against ethanol-induced gastric mucosal injury in mice. This effect may be partially mediated by the efficient wound repair of epithelial cells via increased PGE2 expression.

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