RESUMO
BACKGROUND: Capillary structural abnormalities cause skin disorders. Mottled redness, i.e., skin redness unevenness, may appear on the sun-exposed skin, suggesting capillary structural abnormalities, although its mechanism remains unclear. OBJECTIVE: To observe the capillary structures in the sun-exposed skin where skin redness unevenness is likely to occur, and clarify the mechanism of capillary structural abnormalities. METHODS: The tissue structures in the skin with skin redness unevenness were observed by LC-OCT. Subsequently, immunostaining of the sun-exposed skin where skin redness unevenness is often observed, was performed. Vascular endothelial cells were UV-irradiated to analyze the expression and functions of genes involved in the capillary structures and morphogenesis. RESULTS: The skin with skin redness unevenness exhibited scattering of dilated tubular tissue and disturbance of distribution uniformity. Immunostaining of the sun-exposed skin that were more likely to be exposed to UV rays also revealed similarly disorder of capillary structures. In addition, UVA-irradiated vascular endothelial cells exhibited increased expression of ETBR, involved in telangiectasia, decreased expression of BMPR2, involved in the morphogenesis and maintenance of the blood vessels, and reduced migration of the capillaries. CONCLUSION: UV rays alter ETBR and BMPR2 expression in the skin capillaries, and cause partial dilation and decreased migration, resulting in capillary structural abnormalities and causing skin redness unevenness.
Assuntos
Capilares , Células Endoteliais , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/metabolismo , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Eritema , Humanos , PeleRESUMO
Although ultraviolet (UV) rays cause premature aging of human skin, which is called photoaging, its detailed mechanisms are not known. Stratifin (SFN), a member of the 14-3-3 protein family, is secreted by keratinocytes on human skin, and has an effect on gene expression in other cells. In this study, the association of SFN with the mechanism of photoaging was investigated. The effect of UVB irradiation on SFN expression in epidermal keratinocytes was examined by in vitro and in vivo studies. In addition, the effects of SFN on epidermal keratinocytes and dermal fibroblasts were examined. SFN mRNA expression and protein levels increased significantly in UVB-irradiated keratinocytes. SFN significantly decreased filaggrin and serine palmitoyltransferase mRNA expression in epidermal keratinocytes and hyaluronan synthase 2 mRNA expression in dermal fibroblasts. In addition, it was reconfirmed that SFN induces the downregulation of collagen content through changes of COL-1, MMP-1 and MMP-2 mRNA expressions. Furthermore, the expression level of SFN mRNA was significantly higher in sun-exposed compared with that in sun-shielded skin. These results suggest that SFN affects the water-holding capacity, barrier function and dermal matrix components in photoaging skin. An increase of SFN triggered by UVB irradiation may be one of the causes of alterations observed in photoaging skin.
Assuntos
Proteínas 14-3-3/metabolismo , Proteínas 14-3-3/efeitos da radiação , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/efeitos da radiação , Exorribonucleases/metabolismo , Exorribonucleases/efeitos da radiação , Envelhecimento da Pele/efeitos da radiação , Raios Ultravioleta/efeitos adversos , Proteínas 14-3-3/genética , Biomarcadores Tumorais/genética , Linhagem Celular , Colágeno Tipo I/genética , Epiderme/metabolismo , Epiderme/efeitos da radiação , Exorribonucleases/genética , Fibroblastos/metabolismo , Fibroblastos/efeitos da radiação , Proteínas Filagrinas , Expressão Gênica/efeitos da radiação , Glucuronosiltransferase/genética , Humanos , Hialuronan Sintases , Técnicas In Vitro , Queratinócitos/metabolismo , Queratinócitos/efeitos da radiação , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 2 da Matriz/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Envelhecimento da Pele/fisiologiaRESUMO
Skin pigmentation is caused by various physical and chemical factors. It might also be influenced by changes in the physiological function of skin with aging. Nicotinamide adenine dinucleotide (NADH) dehydrogenase is an enzyme related to the mitochondrial electron transport system and plays a key role in cellular energy production. It has been reported that the functional decrease in this system causes Parkinson's disease. Another study reports that the amount of NADH dehydrogenase in heart and skeletal muscle decreases with aging. A similar decrease in the skin would probably affect its physiological function. However, no reports have examined the age-related change in levels of NADH dehydrogenase in human skin. In this study, we investigated this change and its effect on skin pigmentation using cultured human epidermal keratinocytes. The mRNA expression of NDUFA1, NDUFB7, and NDUFS2, subunits of NADH dehydrogenase, and its activity were significantly decreased in late passage keratinocytes compared to early passage cells. Conversely, the mRNA expression of melanocyte-stimulating cytokines, interleukin-1 alpha and endothelin 1, was increased in late passage cells. On the other hand, the inhibition of NADH dehydrogenase upregulated the mRNA expression of melanocyte-stimulating cytokines. Moreover, the level of NDUFB7 mRNA was lower in pigmented than in nonpigmented regions of skin in vivo. These results suggest the decrease in NADH dehydrogenase with aging to be involved in skin pigmentation.
Assuntos
Queratinócitos/enzimologia , NADH Desidrogenase/metabolismo , Envelhecimento da Pele , Pigmentação da Pele , Células Cultivadas , Complexo I de Transporte de Elétrons , Endotelina-1/efeitos dos fármacos , Endotelina-1/metabolismo , Humanos , Interleucina-1alfa/metabolismo , Melaninas/biossíntese , NADH Desidrogenase/efeitos dos fármacos , NADH NADPH Oxirredutases/metabolismo , RNA Mensageiro/metabolismo , Rotenona/farmacologia , Pele/metabolismo , Estatísticas não Paramétricas , Desacopladores/farmacologiaRESUMO
Transcription factors belonging to the forkhead box gene, group O (FOXOs) family have been found to be crucial in downstream suppression of life-shortening effects of the insulin/insulin-like growth factor-1 (IGF-1) signaling pathway, which accelerates aging by suppressing FOXOs. Thus, FOXOs could hold the key for counteracting aging. Although FOXOs may play a critical role in aging, the effects of FOXOs on UV-induced changes of collagen metabolism by dermal fibroblasts are unknown. In this study, UV-induced changes in FOXO1a expression and the roles of FOXO1a in the regulation of collagen synthesis and matrix metalloproteinase (MMPs) expression in human dermal fibroblasts were investigated. In UVA- or UVB-irradiated fibroblasts, the expression of FOXO1A mRNA decreased significantly. The expression of type I collagen (COLIAI) also decreased. On the other hand, MMP-1 and MMP-2 mRNA levels increased. FOXO1A-small interfering RNA transfection induced the downregulation of FOXO1A expression, it also induced a decrease in COLIAI expression, and it increased MMP-1 and MMP-2 expression. These changes are similar to those observed in UV-irradiated fibroblasts. Furthermore, FOXO1a-peptide induced opposite changes in COLIAI, MMP-1, and MMP-2 expression. Therefore, FOXO1a is involved in the UV-induced changes of type I collagen and MMPs expression.Journal of Investigative Dermatology Symposium Proceedings (2009) 14, 60-62; doi:10.1038/jidsymp.2009.2.
Assuntos
Colágeno/metabolismo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Pele/metabolismo , Pele/efeitos da radiação , Raios Ultravioleta/efeitos adversos , Sequência de Bases , Linhagem Celular , Colágeno Tipo I/genética , Cadeia alfa 1 do Colágeno Tipo I , Primers do DNA/genética , Fibroblastos/metabolismo , Fibroblastos/efeitos da radiação , Proteína Forkhead Box O1 , Fatores de Transcrição Forkhead/antagonistas & inibidores , Expressão Gênica/efeitos da radiação , Humanos , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 2 da Matriz/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismoRESUMO
Increased intracellular concentrations of the initiator protein Rep (or RepA) interfere with pSC101 DNA replication, and mutated Rep proteins that result in an increase in plasmid copy numbers do not inhibit the replication. A rep mutant (rep(inh)) defective in the inhibitory activity was isolated and found to be a new high copy number mutant. The inhibitory function of Rep was enhanced by the coexistence of directly repeated sequences (DR; iterons) in the replication origin region (ori), but not by the inverted repeat sequences (IR) in ori and the rep promoter. This synergistic effect of Rep and DR sequences for the replication inhibition was dependent on their intracellular concentrations. Considering that DR sequences are the specific binding sites of the Rep monomer form, the Rep monomer-DR complex might be responsible for the inhibition of the plasmid replication. Furthermore, the Rep monomer in the crude cell extracts facilitated dimerization of DR DNA fragments by DNA ligase. Neither synergistic inhibitory function with DR nor Rep mediated dimerization of DR DNA was observed in high copy number mutant Rep proteins. The role of the Rep-iteron complex in the copy number control of pSC101 is discussed.