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Expression Of Matrix Metalloproteinases In Intense Pulsed Light Irradiated Normal And Photoaging Skin

Posted on:2011-07-22Degree:DoctorType:Dissertation
Country:ChinaCandidate:W J GuFull Text:PDF
GTID:1114360308959624Subject:Dermatology and Venereology
Abstract/Summary:PDF Full Text Request
Premature skin aging that occurs from excessive exposure to solar ultraviolet light is referred to as photoaging, which is histologically characterized by loss of mature collagen I or elastic fibers. Many modulators and enzymatic reaction are involved in this process. Among these modulators, matrix metalloproteinase(MMP)and tissue inhibitor of metalloproteinase(TIMPs)are the most important ones. It has been reported that the imbalance between MMP and TIMP was closely linked to the histopathological changes of in photoaged skin.IPL technique is a new non-ablative method for treating photoaged skin. Histological studies revealed accumulation of procollagen I, procollagen III after IPL treatment, which was considered as a result of reactive ECM(extracellular matrix)remodeling by IPL induced selective thermal damage. The role of MMPs/TIMPs involved in IPL irradiation remains unknown.Eleven healthy female volunteers were recruited in this study. The normal skin and UVA induced photoaging skin in buttock were irradiated by therapeutical dose of IPL. The skins were divided into five subgroups: group of normal control skin; IPL irradiated normal skin; UVA induced photoaging skin; spontaneously recovered photoaging skin; IPL irradiated photoaging skin. Skin biopsies were taken and protein/mRNA expressions of collagen I/III, elastic fibers and MMP-1, -3, -9, -12, TIMP-1 were examined by histochemistry, immunohistochemistry, image analysis and real time quantitative polymerase chain reaction (qRT-PCR). The data were analyzed and the mechanism was investigated.The results:(1) Compared with the normal control skin, more compactly arranged collagen I fibers and increased protein/mRNA levels of collagen I (p﹤0.05, p﹤0.01) were detected in IPL irradiated normal skin. There were significant elevations of MMP-1, -3, -9, -12, TIMP-1 at protein level (p﹤0.01, p﹤0.01, p﹤0.01, p﹤0.01, p﹤0.01), and at mRNA level (p﹤0.01, p﹤0.01, p﹤0.01, p﹤0.05, p﹤0.05).(2) Compared with the normal control skin, there were fragment of elastic fibers and larger interspaces between collagen I/III fibers in UVA induced photoaging skin. There were significant elevation of MMP-1, -3, -9, -12, TIMP-1 at protein level (p﹤0.01, p﹤0.01, p﹤0.01, p﹤0.01, p﹤0.01), and at mRNA level (p﹤0.01, p﹤0.01, p﹤0.05, p﹤0.01, p﹤0.05).(3) Compared with the notably elevated MMP-9 in IPL irradiated normal skin, the elevation of MMP-1, -3, -12 was prominent in UVA induced photoaging skin. (4) In the spontaneously recovered photoaging skin, protein/mRNA levels of MMP-1, -3, -12 deceased (p﹤0.01, p﹤0.01, p﹤0.01) but that of MMP-9 and TIMP-1 increased (p﹤0.05, p﹤0.05) after 10 weeks recovery. The fragmented elastic fibers and sparsely arranged collagen fibers also recovered.(5) Compared with the spontaneously recovered photoaging skin, there were elevated collagen I mRNA levels and more compact arrangement of collagen I/III fibers in IPL irradiated photoaging skin. IPL also induced significant elevation of MMP-1, -3, -9, -12, TIMP-1 protein level (p﹤0.01, p﹤0.01, p﹤0.01, p﹤0.05, p﹤0.01) and mRNA levels (p﹤0.01, p﹤0.05, p﹤0.01, p﹤0.05, p﹤0.01)Conclusion:(1) IPL caused general elevatins of MMPs/TIMP-1 in human skin, similar to the effect of UVA, which indicated the damage effects of IPL on human skin.(2) IPL and UVA irradiation induced different alteration of ECM proteins. This may be explained by the different wavelength and action mode of IPL and UVA. The differences in MMP expression patterns between IPL and UVA irradiated skin may also play a role in the process of photoaging and photorejuvenation.(3) Spontaneous recovery caused downregulation of MMP-1, -3, -12 but elevation of MMP-9 and TIMP-1. Downregulation of MMP-1, -3, -12 indicated that the alteration of MMPs in photoaging skin was reversible. Elevation of MMP-9 and TIMP-1 may be the compensated reaction to elevation of MMP-1, -3, -12.(4) Modulation of ECM proteins and MMPs/TIMP-1 were similar in IPL irradiated normal skin and IPL irradiated photoaging skin but the extent differs. This may be caused by the different skin color, which contributes to different absorption of IPL.
Keywords/Search Tags:matrix metalloproteinase, intense pulsed light, extracellular matrix
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