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 journalArticle

43 Citations (Scopus)

Abstract

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
Volume49
Issue number2
DOIs
StatePublished - Sep 2010

Fingerprint

Matrix Metalloproteinase 2
Melatonin
Stomach Ulcer
Indomethacin
Vascular Endothelial Growth Factor A
Stomach
Up-Regulation
Matrix Metalloproteinase 14
Metalloproteases
Gastric Mucosa
Cornea
Blood Vessels
Anti-Inflammatory Agents
Antioxidants

Keywords

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

ASJC Scopus subject areas

  • Endocrinology

Cite this

Melatonin promotes angiogenesis during protection and healing of indomethacin-induced gastric ulcer : Role of matrix metaloproteinase-2. / Ganguly, Krishnendu; Sharma, Anamika Vivek; Reiter, Russel J; Swarnakar, Snehasikta.

In: Journal of Pineal Research, Vol. 49, No. 2, 09.2010, p. 130-140.

Research output: Contribution to journalArticle

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