| Hypertrophic scar (HS) is one of the major unsettled clinical problems that due to abnormal proliferation of fibroblast and excessive deposition of extracellular matrix. The scars most commonly occur when epithelialization has been delayed during, foe example, the healing of deep dermal burn wounds. The HS are thick and raised and often darker in color than surrounding skin, moreover, that are frequently associated with pruritus and pain. Therefore, it is significant that exploring the mechanism of HS formation to look for effective prevention and treatment. Many published reports documented the mechanism and advocated a variety of therapies; however, few studies provide a coherent therapeutic plan.Collagen remodeling during the transition from granulation tissue to hypertrophic scar is dependent on continued synthesis and catabolism of collagen at a low rate. The degradation of collagen in the wound is controlled by several proteolytic enzymes termed matrix metalloproteinases (MMPs), which are secreted by macrophages, epidermal cells, and endothelial cells, as well as fibroblasts. The various phases of wound repair rely on distinct combinations of matrix metalloproteinases and tissue inhibitors of metalloproteinases (TIMPs). When MMPs gene expression was examined in fetal scarless and scarring rat skin wounds, an increase in expression occurred. However, the magnitude of this increase was greater in scarless fetal wounds than in scarring wounds. Moreover, expression of the tissue inhibitor of metalloproteinases (TIMPs) was higher in the scarred wounds, suggesting that the MMP/TIMP activity ratio maybe higher in scarless wounds. The production of MMPs and their associated inhibitors produces a delicate balance between matrix deposition and degradation. Subtle differences in MMP activity in fetal wounds may therefore tip this balance, allowing more rapid ECM turnover, which maybe necessary for scarless repair. Increased TIMP and decreased MMP expression has been implicated in diseases of excessive fibrosis and extracellular matrix deposition, such as scleroderma.Hepatocyte growth factor (HGF) can be produced by various cells, including fibroblasts, epithelial and endothelial cells, Kupffer's cells and fat-storing cells in the liver, and malignant cells such as lung and pancreatic carcinoma and leukaemic cell lines. Although earlier studies implicated HGF in embryo development and in promoting tissue regeneration after acute injury, evidence is now emerging that HGF is also an intrinsic antifibrotic factor that plays a critical role in preventing tissue fibrosis in various animal models. Over the past several years, progress has been made in identifying the cellular targets of HGF and in unraveling the molecular mechanisms that underlie its action in tissue fibrosis. One of the anti-fibrogenic effects of HGF is thought to be expressed by the induction of matrix metalloproteinases (MMPs)In this study, it was hypothesised by the author that HGF, a soluble cytokine, could paly an important role to ease hypertrophic scar. But it is not clear that wheather HGF and its receptor c-met, a receptor tyrosine kinases (RTK), expression differs between hypertrophic scars and normal skins. Moreover, the exprssion of MMP-1, MMP-9, TIMP-1, and TIMP-2 of fibroblasts in vitro in adition with/without HGF were investigated to verify the hypothesis.Method: Hypertrophic scar tissues were obtained from 5 asian patients who had deeply burns on the limb or face. Immunohistochemistry procedure was used to investgae the localization an expressiong of HGF/c-met. HS fibroblasts were isolated and cultured by routine method. After identifaction, the 3-7 generation cells could be used. The concentrations of HGF for experimental group were: 25ug/ml, 50 ug/ml and 75 ng/ml.Detecting indexes:1. Immunohistochemistry and computer-assist image analysis technology were used to detect localization an expressiong of HGF/c-met.2. Detecting the cell proliferation curve using the method of MTT.3. immunocytochemistry identified the cultured cell with vimentin monoclone antibody.4. 3H-Proline dope procedure was used to detect the quantum variation of colleagen.5. RT-PCR to checked the transcription of mRNA ofâ… ,â…¢type collagen and CTGF 6. Westernblot detected MMP-1,MMP-2, MMP-9, TIMP-1, TIMP-3, c-jun.Result:1. In both hypertrophic scar and normal skin groups, intense HGF-positive and c-met-positive cells locating at the epidermis were oberved. There was an increase in the number of HGF-positive and c-met-positive cells in granulation tissue at the dermis in the hypertrophic scar tissue groups but not in the control group. The HGF-positive cells in the tissues detected in both groups were probably mainly fibroblasts as judged by their morphology.2. The result of MTT with immunocytochemistry showed that the culltured HSFb met the expriment requirment.3. By administration of HGF, collagen synthesis of experimental HSFb decreased with the relationship with the dose.4. HGF could inhibit the transcription of mRNA ofâ… type collagen,â…¢type collagen and CTGF.7. HGF could enhance the expression of MMP-1, MMP-9 and c-jun.8. HGF could inhibit the MMP-2, TIMP-1, TIMP-3expression of HSFb.9. HGF could acive the ERK 1/2 signal transduction pathway.Conclusion:HGF expression up-regulated in hypertrophic scar fibroblasts could change the colleagen metabolism via inhibiting the expression of colleagen gene, improving the MMP/TIMP. ERK 1/2 signal transduction pathway was activated by HGF to produce the complicate effect.
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