Melatonin promotes angiogenesis during protection and healing of indomethacin-induced gastric ulcer: Role of matrix metaloproteinase-2

Krishnendu Ganguly, Anamika Vivek Sharma, Russel J. Reiter, Snehasikta Swarnakar

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


Matrix metalloproteinase (MMP)-2 is considered as a crucial regulator of angiogenesis, a process of new blood vessel formation. We reported previously that melatonin (N-acetyl-5-methoxy tryptamine), an antioxidant and anti-inflammatory agent, prevents indomethacin-induced gastric ulcers. Herein, we investigated the effect of melatonin on MMP-2-mediated angiogenesis during gastroprotection. Angiogenic properties of melatonin were tested in both rat corneal micropocket assay and in mouse model of indomethacin-induced gastric lesions. Melatonin augmented angiogenesis that was associated with amelioration of MMP-2 expression and activity and, upregulation of vascular endothelial growth factor (VEGF) in rat cornea. Melatonin prevented gastric lesions by promoting angiogenesis via upregulation of VEGF followed by over-expression of MMP-2. Similarly, healing of gastric lesions was associated with early expression of VEGF followed by MMP-2. In addition, upregulation of MMP-2 was parallel to MMP-14 and inverse to tissue inhibitor of metalloprotease (TIMP)-2 expression during gastroprotection. Our data demonstrated that melatonin exerts angiogenesis through MMP-2 and VEGF over-expression during protection and healing of gastric ulcers. This study highlights for the first time a phase-associated regulation of MMP-2 activity in gastric mucosa and an angiogenic action of melatonin to rescue indomethacin-induced gastropathy.

Original languageEnglish (US)
Pages (from-to)130-140
Number of pages11
JournalJournal of pineal research
Issue number2
StatePublished - Sep 2010
Externally publishedYes


  • angiogenesis
  • extracellular matrix
  • indomethacin
  • matrix metalloproteinase
  • melatonin
  • tissue inhibitor of metalloproteinase
  • vascular endothelial growth factor

ASJC Scopus subject areas

  • Endocrinology


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