title: Curcumin heals indomethacin-induced gastric ulceration by stimulation of angiogenesis and restitution of collagen fibers via VEGF and MMP-2 mediated signaling.
abstract: OBJECTIVE
  We examined the molecular mechanism of curcumin in a preventive and therapeutic model of indomethacin-induced gastric ulceration with regard to angiogenic processes.
  
  
  RESULTS
  Disrupted blood vessels, reduced collagen matrices, and significant (60%) injury to mucosal cells were observed during ulceration. In addition, ulcerated tissues exhibited decreased matrix metalloproteinase (MMP)-2 and vascular endothelial growth factor (VEGF) expression in blood vessels. Interestingly, curcumin blocked ulceration by induction of collagenization and angiogenesis in gastric tissues via upregulation of MMP-2, membrane type (MT) 1-MMP, VEGF, and transforming growth factor (TGF)-β at protein and messenger ribonucleic acid (mRNA) levels. To examine the angiogenic properties of curcumin, we employed a chorioallantoic membrane model and Matrigel assay. During healing, curcumin promoted collagenization and angiogenesis as well as enhanced MMP-2 activity via positive MT1-MMP regulation and negative tissue inhibitor of metalloproteinase-2 regulation.
  
  
  METHODS
  Our study demonstrates that curcumin-mediated healing is associated with increased MMP-2, TGF-β, and VEGF expression and that it plays a pivotal role as an angiogenic modulator by stimulating vascular sprout formation and collagen fiber restoration in ulcerated tissues.
  
  
  CONCLUSIONS
  We conclude that curcumin remodels gastric tissues by restoring the collagen architecture and accelerating angiogenesis.
authors.affiliation: Department of Physiology, Drug Development Diagnostics and Biotechnology Division, Indian Institute of Chemical Biology, Kolkata, India.
authors.forename: Anamika Vivek
authors.initials: AV
authors.lastname: Sharma
authors.forename: Krishnendu
authors.initials: K
authors.lastname: Ganguly
authors.forename: Sumit
authors.initials: S
authors.lastname: Paul
authors.forename: Nilanjana
authors.initials: N
authors.lastname: Maulik
authors.forename: Snehasikta
authors.initials: S
authors.lastname: Swarnakar
mesh_terms: D000818:Animals; D003474:Curcumin / Q000494:pharmacology* / Q000627:therapeutic use; D024022:Fibrillar Collagens / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D024022:Fibrillar Collagens; D061965:Matrix Metalloproteinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D020778:Matrix Metalloproteinase 2; D003474:Curcumin; D007213:Indomethacin