Skin photoaging is a complex, multifactorial process resulting in functional and structural changes of the skin, and different phenotypes from chronological skin aging are well-recognized. Ultraviolet (UV)-irradiated ...Skin photoaging is a complex, multifactorial process resulting in functional and structural changes of the skin, and different phenotypes from chronological skin aging are well-recognized. Ultraviolet (UV)-irradiated hairless mice have been used as a skin photoaging animal model. However, differences in morphology and gene expression patterns between UV-induced and chronological skin changes in this mouse model have not been fully elucidated. Here we investigated differences in histopathology and cytokine expression between UV-irradiated and non-irradiated aged hairless mice to clarify the factor(s) that differentiate photoaging from chronological skin aging phenotypes. Eight-week-old HR-1 hairless mice were divided into UV-irradiated (UV-irradiated mice) and non-irradiated (control mice) groups. Irradiation was performed three times per week for 10 weeks. In addition, 30-week-old HR-1 hairless mice were reared until 70 weeks of age without UV irradiation (aged mice). Histopathologies revealed that the flattening of dermal-epidermal junctions and epidermal thickening were observed only in UV-irradiated mice. Decreases in fine elastic fibers just beneath the epidermis, the thickening of elastic fibers in the reticular dermis, and the accumulation of glycosaminoglycans were more prominent in UV-irradiated mice as compared to non-irradiated aged mice. Quantitative PCR analyses revealed that UV-irradiated mice showed an increase in the expression of IFN-γ. In contrast, aged mice exhibited proportional up-regulation of both pro-inflammatory and anti-inflammatory cytokines. The IFN-γ/IL-4 ratio, an indicator for the balance of pro-inflammatory and anti-inflammatory cytokines, was significantly higher in UV-irradiated mice as compared to control and non-irradiated aged mice. An elevated IFN-γ/IL-4 ratio was also observed in aged senescence-accelerated mouse-prone 1 (SAMP1) mice, a spontaneous skin photoaging model we recently reported. Thus, an imbalance between pro-inflammatory and anti-inflammatory cytokines might be a key factor to differentiate photoaged skin from chronologically-aged skin.展开更多
Hair provides thermal regulation for mammals and protects the skin from wounds,bites and ultraviolet(UV)radiation,and is important in adaptation to volatile environments.Pigs in nature are divided into hairy and hairl...Hair provides thermal regulation for mammals and protects the skin from wounds,bites and ultraviolet(UV)radiation,and is important in adaptation to volatile environments.Pigs in nature are divided into hairy and hairless,which provide a good model for deciphering the molecular mechanisms of hairlessness.We conducted a genomic scan for genetically differentiated regions between hairy and hairless pigs using 60K SNP data,with the aim to better understand the genetic basis for the hairless phenotype in pigs.A total of 38405 SNPs in 498 animals from 36 diverse breeds were used to detect genomic signatures for pig hairlessness by estimating between-population(FST)values.Seven diversifying signatures between Yucatan hairless pig and hairy pigs were identified on pig chromosomes(SSC)1,3,7,8,10,11 and 16,and the biological functions of two notable genes,RGS17 and RB1,were revealed.When Mexican hairless pigs were contrasted with hairypigs,strong signatures were detected on SSC1 and SSC10,which harbor two functionally plausible genes,REV3L and BAMBI.KEGG pathway analysis showed a subset of overrepresented genes involved in the T cell receptor signaling pathway,MAPK signaling pathway and the tight junction pathways.All of these pathways may be important in local adaptability of hairless pigs.The potential mechanisms underlying the hairless phenotype in pigs are reported for the first time.RB1 and BAMBI are interesting candidate genes for the hairless phenotype in Yucatan hairless and Mexico hairless pigs,respectively.RGS17,REV3L,ICOS and RASGRP1 as well as other genes involved in the MAPK and T cell receptor signaling pathways may be important in environmental adaption by improved tolerance to UV damage in hairless pigs.These findings improve our understanding of the genetic basis for inherited hairlessness in pigs.展开更多
文摘Skin photoaging is a complex, multifactorial process resulting in functional and structural changes of the skin, and different phenotypes from chronological skin aging are well-recognized. Ultraviolet (UV)-irradiated hairless mice have been used as a skin photoaging animal model. However, differences in morphology and gene expression patterns between UV-induced and chronological skin changes in this mouse model have not been fully elucidated. Here we investigated differences in histopathology and cytokine expression between UV-irradiated and non-irradiated aged hairless mice to clarify the factor(s) that differentiate photoaging from chronological skin aging phenotypes. Eight-week-old HR-1 hairless mice were divided into UV-irradiated (UV-irradiated mice) and non-irradiated (control mice) groups. Irradiation was performed three times per week for 10 weeks. In addition, 30-week-old HR-1 hairless mice were reared until 70 weeks of age without UV irradiation (aged mice). Histopathologies revealed that the flattening of dermal-epidermal junctions and epidermal thickening were observed only in UV-irradiated mice. Decreases in fine elastic fibers just beneath the epidermis, the thickening of elastic fibers in the reticular dermis, and the accumulation of glycosaminoglycans were more prominent in UV-irradiated mice as compared to non-irradiated aged mice. Quantitative PCR analyses revealed that UV-irradiated mice showed an increase in the expression of IFN-γ. In contrast, aged mice exhibited proportional up-regulation of both pro-inflammatory and anti-inflammatory cytokines. The IFN-γ/IL-4 ratio, an indicator for the balance of pro-inflammatory and anti-inflammatory cytokines, was significantly higher in UV-irradiated mice as compared to control and non-irradiated aged mice. An elevated IFN-γ/IL-4 ratio was also observed in aged senescence-accelerated mouse-prone 1 (SAMP1) mice, a spontaneous skin photoaging model we recently reported. Thus, an imbalance between pro-inflammatory and anti-inflammatory cytokines might be a key factor to differentiate photoaged skin from chronologically-aged skin.
基金supported by National Natural Science Foundation of China(31071089)Program for New Century Excellent Talents in Universities,the National Key Technology R&D Program(2011BAD28B01)Program for Youth Scientist of Jiangxi Province and the earmarked fund for Jiangxi Agriculture Research System and The graduate innovation fund of Jiangxi Province(YC2012-S057).
文摘Hair provides thermal regulation for mammals and protects the skin from wounds,bites and ultraviolet(UV)radiation,and is important in adaptation to volatile environments.Pigs in nature are divided into hairy and hairless,which provide a good model for deciphering the molecular mechanisms of hairlessness.We conducted a genomic scan for genetically differentiated regions between hairy and hairless pigs using 60K SNP data,with the aim to better understand the genetic basis for the hairless phenotype in pigs.A total of 38405 SNPs in 498 animals from 36 diverse breeds were used to detect genomic signatures for pig hairlessness by estimating between-population(FST)values.Seven diversifying signatures between Yucatan hairless pig and hairy pigs were identified on pig chromosomes(SSC)1,3,7,8,10,11 and 16,and the biological functions of two notable genes,RGS17 and RB1,were revealed.When Mexican hairless pigs were contrasted with hairypigs,strong signatures were detected on SSC1 and SSC10,which harbor two functionally plausible genes,REV3L and BAMBI.KEGG pathway analysis showed a subset of overrepresented genes involved in the T cell receptor signaling pathway,MAPK signaling pathway and the tight junction pathways.All of these pathways may be important in local adaptability of hairless pigs.The potential mechanisms underlying the hairless phenotype in pigs are reported for the first time.RB1 and BAMBI are interesting candidate genes for the hairless phenotype in Yucatan hairless and Mexico hairless pigs,respectively.RGS17,REV3L,ICOS and RASGRP1 as well as other genes involved in the MAPK and T cell receptor signaling pathways may be important in environmental adaption by improved tolerance to UV damage in hairless pigs.These findings improve our understanding of the genetic basis for inherited hairlessness in pigs.
