Leptin promotes gastric ulcer healing via upregulation of vascular endothelial growth factor.
OBJECTIVE
Leptin, a key hormone in regulation of food intake and energy expenditure, exerts pleiotropic cytokine-like biological effects. Its role in gastric ulcer healing is unclear. In this study, we investigated the role of leptin in gastric ulcer healing.


METHODS
Experimental gastric ulcer was induced by focal serosal application of acetic acid in leptin-deficient ob/ob mice and wild-type mice. Healing of gastric ulcer and angiogenesis in the ulcer tissue was evaluated.


RESULTS
Gastric ulcer healing was delayed in ob/ob mice compared with that in wild-type mice. The impairment of ulcer healing observed in ob/ob mice was characterized by reduced expression of vascular endothelial growth factor (VEGF) and impairment of angiogenesis. Systemic administration of leptin to ob/ob mice reversed the impairment of gastric ulcer healing; this reversal was accompanied by an increase in VEGF expression and angiogenesis. Although mRNA for leptin was not expressed in normal gastric mucosa and not induced in ulcerous tissue, leptin receptor expression was markedly upregulated in gastric epithelial cells at ulcer margins, and was colocalized with VEGF.


CONCLUSIONS
These findings suggest that leptin promotes gastric ulcer healing by induction of angiogenesis in the granular tissue of ulcers via upregulation of VEGF expression.
Tanigawa
Tetsuya
T
Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan. ttanigawa @ med.osaka-cu.ac.jp
Watanabe
Toshio
T
Otani
Koji
K
Nadatani
Yuji
Y
Machida
Hirohisa
H
Okazaki
Hirotoshi
H
Yamagami
Hirokazu
H
Watanabe
Kenji
K
Tominaga
Kazunari
K
Fujiwara
Yasuhiro
Y
Oshitani
Nobuhide
N
Higuchi
Kazuhide
K
Arakawa
Tetsuo
T
D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D020738:Leptin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D018919:Neovascularization, Physiologic / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000378:metabolism*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D014945:Wound Healing / Q000187:drug effects
D020738:Leptin; D042461:Vascular Endothelial Growth Factor A