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
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
Background: Autoantibodies (Aabs) are the hallmark of numerous systemic autoimmune pathologies (SAPs), for instance anti-Ro/SS-A Aabs are usually found in Systemic Lupus Erythematosus (SLE) and Sjogren’s Syndrome. Cu...Background: Autoantibodies (Aabs) are the hallmark of numerous systemic autoimmune pathologies (SAPs), for instance anti-Ro/SS-A Aabs are usually found in Systemic Lupus Erythematosus (SLE) and Sjogren’s Syndrome. Cutaneous photosensitivity (CP) is found in most forms and subsets of LE and consists of a skin rash as a result of unusual reaction to sunlight. There are many theories which relate specifically the presence of circulating anti-Ro/SS-A Aabs with the CP phenomenon, though there are several studies which are in disagreement. Results: In this study we analyzed the relationship between CP and anti-Ro Aabs by means of two approaches. The first one included an in vitro model where we evaluated by flow cytometry the binding capacity of affinity-purified Aabs to autoantigens relocalized on apoptotic keratinocyte’s surface. We found that there was no relationship between the binding capacity of serum from 10 selected patients or their corresponding purified anti-Ro52 and anti-Ro60 Aabs, and the presence or absence of CP, neither with the SAPs. The in vivo model consisted of Hairless SKH:1 mice which were induced to produce anti-murine Ro52 and/or Ro60 Aabs and were subsequently irradiated with UVB light. We evaluated the skin histology and also the epidermal production of TNF-α. We found no differences between the groups in neither of the parameters evaluated. Conclusions: These results agree with some studies on the role of the Aabs in CP, considering anti-Ro Aabs not as the only responsible for the manifestation;and disagree with many other authors, who believe in the strong association between these two events.展开更多
Animal body coverings provide protection and allow for adaptation to environmental pressures such as heat,ultraviolet radiation,water loss,and mechanical forces.Here,using a comparative genomics analysis of 39 mammal ...Animal body coverings provide protection and allow for adaptation to environmental pressures such as heat,ultraviolet radiation,water loss,and mechanical forces.Here,using a comparative genomics analysis of 39 mammal species spanning three skin covering types(hairless,scaly and spiny),we found some genes(e.g.,UVRAG,POLH,and XPC)involved in skin inflammation,skin innate immunity,and ultraviolet radiation damage repair were under selection in hairless ocean mammals(e.g.,whales and manatees).These signatures might be associated with a high risk of skin diseases from pathogens and ultraviolet radiation.Moreover,the genomes from three spiny mammal species shared convergent genomic regions(EPHB2,EPHA4,and NIN)and unique positively selected genes(FZD6,INVS,and CDC42)involved in skin cell polarity,which might be related to the development of spines.In scaly mammals,the shared convergent genomic regions(e.g.,FREM2)were associated with the integrity of the skin epithelium and epidermal adhesion.This study identifies potential convergent genomic features among distantly related mammals with the same skin covering type.展开更多
Objective:Isolated hereditary hypotrichosis is caused by mutations in as many as 11 different genes.The conventional mutation detection strategy consists of sequencing of individual candidate genes separately,a time c...Objective:Isolated hereditary hypotrichosis is caused by mutations in as many as 11 different genes.The conventional mutation detection strategy consists of sequencing of individual candidate genes separately,a time consuming and costly approach.In this study,we perform genome-wide single nucleotide polymorphism(SNP)array to identify candidate genes of hereditary hypotrichosis.Methods:A consanguineous family with two patients with hereditary hypotrichosis was enrolled,and autozygosity mapping by genome-wide SNP array was utilized to identify candidate genes.Results:Autozygosity mapping delineated runs of homozygosity,and alignment of the 11 genes identified the hairless(HR)gene as the candidate gene.Nucleotide sequencing revealed a novel homozygous mutation c.381delT,p.Ser127ArgfsTer40.Conclusion:This study illustrates how autozygosity mapping by a high-density SNP array streamlines mutation detection in heritable skin diseases.展开更多
Bursicon is a neuropeptide that regulates cuticle sclerotization （hardening and tanning） in insect via a G-protein coupled receptor. However, the signal transduction pathway downstream of the G-protein coupled recep...Bursicon is a neuropeptide that regulates cuticle sclerotization （hardening and tanning） in insect via a G-protein coupled receptor. However, the signal transduction pathway downstream of the G-protein coupled receptor is currently not well known. In our recent microarray analysis, we identified a panel of genes regulated by bursicon in Drosophila. One of the genes, Suppressor of Hairless, or Su（H）, has drawn our attention because its product acts down-stream of the bursicon receptor. In the present study, we cloned the Drosophila homolog, mdSu（H）, from the house fly Musca domestica using 3＇ and 5＇ rapid amplification of complementary DNA ends. Real-time polymerase chain reaction analysis revealed that the level ofmdSu（H） transcript is up-regulated by ~3-fold 1 h after recombinant bursicon injection, which correlates well with the cuticle sclerotization process observed in the recombinant bursicon-injected flies. We infer that Su（H） is an essential gene involved in the insect cuticle sclerotization process.展开更多
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.
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.
文摘Background: Autoantibodies (Aabs) are the hallmark of numerous systemic autoimmune pathologies (SAPs), for instance anti-Ro/SS-A Aabs are usually found in Systemic Lupus Erythematosus (SLE) and Sjogren’s Syndrome. Cutaneous photosensitivity (CP) is found in most forms and subsets of LE and consists of a skin rash as a result of unusual reaction to sunlight. There are many theories which relate specifically the presence of circulating anti-Ro/SS-A Aabs with the CP phenomenon, though there are several studies which are in disagreement. Results: In this study we analyzed the relationship between CP and anti-Ro Aabs by means of two approaches. The first one included an in vitro model where we evaluated by flow cytometry the binding capacity of affinity-purified Aabs to autoantigens relocalized on apoptotic keratinocyte’s surface. We found that there was no relationship between the binding capacity of serum from 10 selected patients or their corresponding purified anti-Ro52 and anti-Ro60 Aabs, and the presence or absence of CP, neither with the SAPs. The in vivo model consisted of Hairless SKH:1 mice which were induced to produce anti-murine Ro52 and/or Ro60 Aabs and were subsequently irradiated with UVB light. We evaluated the skin histology and also the epidermal production of TNF-α. We found no differences between the groups in neither of the parameters evaluated. Conclusions: These results agree with some studies on the role of the Aabs in CP, considering anti-Ro Aabs not as the only responsible for the manifestation;and disagree with many other authors, who believe in the strong association between these two events.
基金supported by the National Natural Science Fund for Outstanding Youth Fund(31222009,31272295,31570489,81622048 and 81473377)the Project of Quality Guarantee System of Chinese Herbal Medicines(201507002)+1 种基金Science Foundation for Distinguished Young Scholars of Jiangsu Province(BK20140049)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘Animal body coverings provide protection and allow for adaptation to environmental pressures such as heat,ultraviolet radiation,water loss,and mechanical forces.Here,using a comparative genomics analysis of 39 mammal species spanning three skin covering types(hairless,scaly and spiny),we found some genes(e.g.,UVRAG,POLH,and XPC)involved in skin inflammation,skin innate immunity,and ultraviolet radiation damage repair were under selection in hairless ocean mammals(e.g.,whales and manatees).These signatures might be associated with a high risk of skin diseases from pathogens and ultraviolet radiation.Moreover,the genomes from three spiny mammal species shared convergent genomic regions(EPHB2,EPHA4,and NIN)and unique positively selected genes(FZD6,INVS,and CDC42)involved in skin cell polarity,which might be related to the development of spines.In scaly mammals,the shared convergent genomic regions(e.g.,FREM2)were associated with the integrity of the skin epithelium and epidermal adhesion.This study identifies potential convergent genomic features among distantly related mammals with the same skin covering type.
文摘Objective:Isolated hereditary hypotrichosis is caused by mutations in as many as 11 different genes.The conventional mutation detection strategy consists of sequencing of individual candidate genes separately,a time consuming and costly approach.In this study,we perform genome-wide single nucleotide polymorphism(SNP)array to identify candidate genes of hereditary hypotrichosis.Methods:A consanguineous family with two patients with hereditary hypotrichosis was enrolled,and autozygosity mapping by genome-wide SNP array was utilized to identify candidate genes.Results:Autozygosity mapping delineated runs of homozygosity,and alignment of the 11 genes identified the hairless(HR)gene as the candidate gene.Nucleotide sequencing revealed a novel homozygous mutation c.381delT,p.Ser127ArgfsTer40.Conclusion:This study illustrates how autozygosity mapping by a high-density SNP array streamlines mutation detection in heritable skin diseases.
文摘Bursicon is a neuropeptide that regulates cuticle sclerotization （hardening and tanning） in insect via a G-protein coupled receptor. However, the signal transduction pathway downstream of the G-protein coupled receptor is currently not well known. In our recent microarray analysis, we identified a panel of genes regulated by bursicon in Drosophila. One of the genes, Suppressor of Hairless, or Su（H）, has drawn our attention because its product acts down-stream of the bursicon receptor. In the present study, we cloned the Drosophila homolog, mdSu（H）, from the house fly Musca domestica using 3＇ and 5＇ rapid amplification of complementary DNA ends. Real-time polymerase chain reaction analysis revealed that the level ofmdSu（H） transcript is up-regulated by ~3-fold 1 h after recombinant bursicon injection, which correlates well with the cuticle sclerotization process observed in the recombinant bursicon-injected flies. We infer that Su（H） is an essential gene involved in the insect cuticle sclerotization process.
