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The Role And Mechanisms Of Cell Proliferation Negative Factor P16 And Op18 In Burn Wound Healing And Scar Formation

Posted on:2005-06-28Degree:DoctorType:Dissertation
Country:ChinaCandidate:Q J YaoFull Text:PDF
GTID:1104360122495808Subject:Surgery
Abstract/Summary:PDF Full Text Request
Pathological scar including hypertrophic scar(HTS) and keloid is a special phenomenon of human being wound healing. Many kinds of cells are involved in wound healing, the abnormal biological action of fibroblasts, especially abnormal proliferation of fibroblasts plays important role in scar formation. Overgrowth of fibroblasts leads to excessive collagen depositing, and the collagen orientation appears in derangement, thus malformation and dysfunction of different extent emerges after wound healing. Many vivo and vitro factors influence the results of wound healing and the extent of scar formation. Except surgical operation, it is short of effective ways to prevent scar formation. There were many studies on wound healing and scar formation in recent years, but there was no breaking progress of theories on wound healing and scar formation. Some basic problems are still upsetting clinical doctors: Will those products made by gene engineering which could accelerate wound healing cause excessive scar formation? Is it possible to apply medicine to control scar in early stage? How can we prevent scar formation and accelerate wound healing at the same time? As for fibroblast proliferation, accelerating wound healing and preventing scar formation ear just like the two sides of a coin, relative equilibrium of positive and negative regulation will control a fitness fibroblast proliferation, and it may be an ideal model of wound healing. Up till now, there is no study of negative regulation mechanisms on wound healing and scar formation.With the development of modern cellular biology and molecular biology, relations between gene and disease are disclosed one by one. Gene heredity has compact relation with the beginning, susceptibility and medicine sensitivity of disease. Different gene shows different expression at the different phase of disease. Excessive scar which is one special kind of diseases on human being must have special gene expression. Gene expression map and single gene expression of the gene map are changing continually, it formed the complicated, web-like and relatively balanced regulatory mechanism of wound healing and scar formation. In fact, that excessive scar formed is because of the dysequilibrium of regulation mechanism of fibroblast. In recentyears, studies showed that oncogenesis is because of overgrowth of tumor cells. Scargenesis is similar to oncogenesis, scar and tumor may have same or similar developing and regulatory mechanism, so it is available to apply the regulatory mechanism of tumor to scar. Oncogenesis is mainly because of the dysequilibrium of negative regulation mechanism, and suppressor gene p16 plays important role on negative regulation mechanism of tumor. Some studies indicated that there was abnormal expression of suppressor gene in excessive scar. Negative regulation is urgent and realistic to the basic theory of wound healing and clinic therapy. So suppressor gene p16 was chosen as the target in this study.p16 gene appears deletion, mutation and increased methylation in tumor, if p16 gene appears complete deletion, there was no p16 protein in tumor; if p16 gene appears partial deletion, mutation, no function or partial function p16 protein appears in tumor. More increased methylation of p16 gene will cause less p16 protein. Gene deletion can be detected by PCR of genome, and gene mutation can be detected by PCR-SSCP, and methylation can be detected by MS-PCR. RT-PCR and Western blot can detect gene and protein expression respectively. We dynamically detected p16 gene and protein expression in deep second degree burn wound, include early phase of deep second degree burn healing and different phase of hypertrophic scar, we also detected that in different scars (stable scar, keloid, scar around bedsore).Skin graft can effectively prevent scar formation, but skin graft time and skin graft thickness have compact relation with the extent of scar formation. Fibroblast proliferation changes after skin graft. Skin graft may change the negative regulatory mechanism of fibroblast. In...
Keywords/Search Tags:wound healing, scar, burn model, tumor suppressor gene, p16, oncoprotein 18, gene expression, gene mutation
PDF Full Text Request
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