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Melatonin promotes angiogenesis during protection and healing of indomethacin‐induced gastric ulcer: role of matrix metaloproteinase‐2
Author(s) -
Ganguly Krishnendu,
Sharma Anamika Vivek,
Reiter Russel J.,
Swarnakar Snehasikta
Publication year - 2010
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2010.00776.x
Subject(s) - melatonin , angiogenesis , matrix metalloproteinase , downregulation and upregulation , wound healing , vascular endothelial growth factor , tissue inhibitor of metalloproteinase , neovascularization , endocrinology , matrix metalloproteinase inhibitor , medicine , pharmacology , chemistry , immunology , vegf receptors , biochemistry , gene
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.