Font Size: a A A

Exploration Of Related Genes And Mechanism Involved In Skin Photoaging & Estrogen-associated Intrinsic Skin Aging Of Chinese Han Female

Posted on:2012-02-06Degree:DoctorType:Dissertation
Country:ChinaCandidate:W YanFull Text:PDF
GTID:1114330338470298Subject:Surgery
Abstract/Summary:
Background and Objective Skin aging can be classified into intrinsic aging and extrinsic aging. The latter is mainly influenced by ultraviolet, including UVA and UVB, known as photoaging. Photoaging is first characterized with the alteration in wrinkles, analosis and dyspigmentation, et al, and then the photoaging will develop into severe skin diseases, even skin tumour. Although significant advances in recent years have been made in both the organ culture of skin, little is known in detail about the biological processes and the genes involved in them, especially in Chinese Ham females'skin. Further more, most of these studies are mainly focused on some skin cell (e.g fibroblast, keratinocyte, or melanocytes) or some subunit of skin only (e.g epidermis, dermis, or connective tissue), ignoring the whole biological network based on complete skin tissue. Our study is designed to find out all possible genes and biologic processes involved in skin photoaging based on Chinese Han female full-thickness skin at by microarray technology.Methods 21 healthy Chinese Han women were recruited from Plastic Surgery Hospital of PUMC, Beijing, China. All subjects were similar in photoaging degree, living and climate condition, hair style, and all subjects were healthy without special aging related family history nor smoking and alcoholism history. All skin samples were obtained from the abandoned skin tissue of pre-auricular (UV explosed) and post-auricular (UV protected) during rhytidectomy surgery and were made into full-thickness skin for further research. Illumina beadchips were used for differentially expressed genes analysis. The differentially expressed genes were then analysed in functional clustering with GO database and functional enriched with WebGestalt, DAVID, and GSEA. Q-RT-PCR was applied to further confirmed the chosen genes.Results Identification of the DEGs among these expressed genes then yielded 1762 genes (up-regulated 829 genes, down-regulated 933 genes), which passed the cutoff of P<0.05. All genes were annotated and functional clustered with GO gene database into immune response, cell adhension and receptor related, signal transduction, transcription regulation, inflammation, enzyme related, mental iron binding, collagen and fibrin, cell apoptosis, vasculogenesis, cell proliferation,differentiation, and development, skin development, metabolism, et al. All the genes were functional enriched with analysis tools of WebGestalt, DAVID, GSEA and KEGG database into 11 different pathway, such as ECM-receptor interaction (ECM), TGF-beta signaling pathway (TGF), Cell cycle (CC),Valine, leucine and isoleucine degradation (VLI), Arginine and proline metabolism (APM), Fructose and mannose metabolism (FMM), Glycolysis/ Gluconeogenesis (GG), Glycosphingolipid biosynthesis-ganglioseries (GBG), Tryptophan metabolism (TM), Arachidonic acid metabolism (AAM), Nitrogen metabolism (NM)Lysine degradation, Beta-Alanine metabolism, MAPK signaling pathway, Insulin signaling pathway, Citrate cycle(TCA cycle), mRNA degradation, et al. Five genes, HOXA5,LEPR,CLDN5,LAMC3 and CGA, were chosen for further confirmed by Q-RT-PCR and the Results of the quantitative RT-PCR demonstrated concordance in direction of change between the two different platforms.Conclusion Our study reveals that skin photoaging is a complex biological process with many genes and biological pathway involved in it. Except few genes and pathway reported in the past research, there is still a great difference in results between the present and previous studies. Most of the related genes and biological pathways involved in this field haven't been reported yet till now. We carried out this study based on full-thickness skin, focusing more on the biological processes network in the whole skin tissue, which provided us more believable and comprehensive information about skin photoaging of Chinese Han female. It will provide us insight information about the effect of skin photoaging and skin photoaging related skin diseases. Our study is a only display of the skin photoaging related genes and pathways. Further study is needed to investigate the biological functions genes and related biological pathway in skin photoaging. Background and Objective The skin is a mirror of the aging process in human. Skin aging can be classified into extrinsic aging and intrinsic aging. The latter is mainly influenced by genetic factor-induced or alterations of the endocrine environment-induced. Estrogen, as one of the sex hormone, plays an important role in intrinsic skin aging, especially in the skin aging of menopausal women. In women, estrogen levels decline rapidly at menopaluse as a result of the loss of ovarian follicles and decrease gradually with the age. This change will accelerate skin aging. It leads to the alternations in skin of dryness, atrophy, fine wrinkling, and hot flashes. Many studies have proved the positive corelation between estragon and intrinsic skin aging directly, and the availability of hormone replacement treatment (HRT) also demonstrates the beneficial effect of estrogen in skin aging indirectly too. Although significant advances in recent years have been made in both the organ culture of skin, little is known in detail about the biological processes and the genes involved in them, especially in Chinese Ham females'skin. Further more, most of these studies are mainly focused on some skin cell (e.g fibroblast, keratinocyte, or melanocytes) or some subunit of skin only (e.g epidermis, dermis, or connective tissue), ignoring the whole biological network based on complete skin tissue. Our study is designed to find out all possible genes and biologic processes involved in estrogen-associated intrinsic skin aging based on Chinese Han female full-thickness skin by microarray technology.Methods 13 healthy Chinese Han women (age ranged 46-55y, average age 50.7y) were recruited from Plastic Surgery Hospital of PUMC, Beijing, China. They were divided into two groups according to their menstrual history. All subjects were healthy without special aging related family history nor smoking and alcoholism history. All skin samples were obtained from the abandoned skin tissue of post-auricular (UV protected) during rhytidectomy surgery and were made into full-thickness skin stored in liquid nitrogen immediately for future research. Illumina beadchips were used for differentially expressed genes analysis. The differentially expressed genes were then analysed in functional clustering and enrichment. Q-RT-PCR was applied to confirmed the chosen genes.Results Identification of the DEGs among these expressed genes then yielded 244 genes (up-regulated 131 genes, down-regulated 113 genes), which passed the cutoff of P<0.05. All 244 genes were annotated and functional clustered with GO gene database into metabolism, cell adhension, mental iron binding, transcription, signal transduction, cell apoptosis, biosynthesis, ubiquitin cycle, immune response, inflammation, development, et al. All the 244 genes were functional enriched with WebGestalt tool and KEGG database into 11 different pathway, such as Lysine degradation, Beta-Alanine metabolism, MAPK signaling pathway, Insulin signaling pathway, Citrate cycle(TCA cycle), mRNA degradation, et al.Conclusion Our study reveals that there is a close correlation between the estrogen and intrinsic skin aging with many genes and biological pathway involved in it. Except few genes and pathway reported in the past research, there is still a great difference in results between the present and previous studies. Most of the related genes and biological pathways involved in this field haven't been reported yet till now. We carried out this study based on full-thickness skin, focusing more on the biological processes network in the whole skin tissue, which provided us more believable and comprehensive information about estrogen-associated intrinsic skin aging of Chinese Han female. It will provide us insight information about the effect of estrogen in skin aging and estrogen-related skin diseases. Further study is needed to investigate the biological functions genes and related biological pathway in estrogen-associated intrinsic skin aging.
Keywords/Search Tags:Photoaging, Ultraviolet, Microarray, Skin, MMPs, Metabolism, Estrogen, Intrinsic aging
Related items