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Wound healing is the result of a complex interplay between various cell types wherein macrophages and fibroblasts play a crucial role during various phases of the process The different phases include hemostasis inflammation cellular migration proliferation wound contraction and remodeling Diegelmann RF 2004 Monaco JL 2003 Both macrophage and fibroblast act as stimulators for several different cell types by producing various signaling factors like Platelet-Derived Growth Factor PDGF Transforming Growth Factor beta TGF- Fibroblast growth factor FGF Nitric Oxide NO Cytokines and Matrix Metalloproteinases MMP Diegelmann RF 2004 Lawrence WT 1994 Impaired wound healing is one of the pathophysiological diseases which affect the quality of life This delay in wound healing may occur due to several reasons like decreased production of growth factors Nitric oxide and cytokines Nitric oxide is produced by the enzyme Nitric oxide synthase NOS which converts L-arginine to L-citrulline It is a small diffusible intercellular molecule which has an important role in wound healing process Luo JD 2005 The enzyme NOS exists in three distinct isoforms such iNOS eNOS and nNOS AldertonWK 2001 iNOS is an inducible enzyme and is initially found in Macrophages Luo JD 2005 NOS are produced via EGFR signaling pathway Liu B 2004 EGFR signaling pathway is involved in many important functions of wound healing like cell proliferation survival and migration EGFR ligand system plays a major role in the defensive response during wound healing and chronic inflammatory skin disorders Pastore S 2008 HB-EGF is one of the epidermal growth factor type ligands which interact with EGF receptors and up regulates eNOS expression leading to the increase in the production of nitric oxide This occurs through the activation of PI3k pathway The nitric oxide released helps in cell migration and angiogenesis Mehta VB 2008 Hepatocyte growth factor HGF is another tyrosine kinase receptor ligand which also up regulates the eNOS expression and nitric oxide synthesis This eNOS phosphorylation is mediated by crosstalk between MAPK and
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