Filaggrin (FLG) plays an important role in the epidermal barrier function, which identified in patients with ichthyosis vulgaris(IV).To study the genetics of FLG mutations in Southern Chinese patients with IV. We eval...Filaggrin (FLG) plays an important role in the epidermal barrier function, which identified in patients with ichthyosis vulgaris(IV).To study the genetics of FLG mutations in Southern Chinese patients with IV. We evaluated the influence of five mutations (3321 delA, 441delA, 1249 insG, E1795X and S3296X) in a cohort of 65 IV Chinese patients and in 100 control individuals using the Sequenom? MassARRAY? system. The null allele frequency of 3321delA was 52.31%(34/65). FLG mutation 441delA was only found in one IV patients. FLG mutations 1249insG, E1795X and S3296X were not found in these patients. These findings show that the mutation 3321delA represent the most frequent genetic cause in Southern Chinese IV patients. Our findings confirm and extend the knowledge of the influence of FLG mutations in IV.展开更多
The relationship between the Filaggrin gene(FLG) rs2065955 polymorphism and susceptibility to Epstein-Barr virus(EBV)-associated gastric carcinoma(EBVa GC) and EBV-negative gastric carcinoma(EBVn GC) was investigated ...The relationship between the Filaggrin gene(FLG) rs2065955 polymorphism and susceptibility to Epstein-Barr virus(EBV)-associated gastric carcinoma(EBVa GC) and EBV-negative gastric carcinoma(EBVn GC) was investigated in Shandong Province,China.We detected the FLG rs2065955 genotype and allele distribution by using PCR and restriction fragment length polymorphism(RFLP) in 64 EBVa GC,82 EBVn GC,and 111 normal control samples.Immunohistochemistry was used to detect the level of FLG protein in 35 EBVa GC and 51 EBVn GC tumor tissues.Compared with normal controls,the genotype CC and allele C of FLG rs2065955 showed higher frequency in EBVa GC and EBVn GC.There was no significant difference between EBVa GC and EBVn GC in allele distribution of FLG rs2065955,but the genotype CC was found more frequently in EBVa GC than in EBVn GC.The risk of developing either EBVa GC or EBVn GC in genotype CC was higher than in other genotypes.Furthermore,genotype CC of FLG rs2065955 may contribute more to the risk of developing EBVa GC than EBVn GC.There was no significant difference in the expression level of FLG protein between EBVa GC and EBVn GC.In conclusion,the FLG rs2065955 polymorphism was significantly related to gastric carcinoma.Allele C of FLG rs2065955 could be a risk factor for EBVa GC or EBVn GC,while genotype CC of FLG rs2065955 was especially associated with EBVa GC.展开更多
The epidermis represents an essential barrier versus a broad range of exogenous stimuli. To form a functional epidermis, keratinocytes express filaggrin which plays a vital role in atopic dermatitis. However the relat...The epidermis represents an essential barrier versus a broad range of exogenous stimuli. To form a functional epidermis, keratinocytes express filaggrin which plays a vital role in atopic dermatitis. However the relationship between filaggrin and other skin diseases remains unknown. In our study we chose 5 different common skin diseases and analyzed the expression of filaggrin in the skin using immunohistochemistry. Imiquimod (IMQ)-induced mouse model was used for detecting the filaggrin level and barrier function. The results indicated that the expression of filaggrin is reduced in psoriasis compared to the other skin diseases. Furthermore in vivo study showed that the skin barrier is defected with a decreased expression of filaggrin in IMQ-induced psoriasis mouse model, which is accompanied with an increased level of IL-17/IL-23. In conclusion, the defective skin barrier is involved in the development of psoriasis in human and mice with a reduced expression of filaggrin which may be regulated by the increased level of IL-17/IL-23 in the skin.展开更多
Objective:Filaggrin(FLG)is a protein expressed in the epidermis and involved in the maintenance of the epidermal barrier.However,the expression and localization of FLG in the upper airway remain controversial.The pres...Objective:Filaggrin(FLG)is a protein expressed in the epidermis and involved in the maintenance of the epidermal barrier.However,the expression and localization of FLG in the upper airway remain controversial.The present study aimed to determine the significance of FLG and the effect of S100A7 on FLG expression in the upper respiratory mucosa.Methods:Human nasal epithelial cells(HNECs)were cultured and examined for FLG expression and S100A7 effects by real-time polymerase chain reaction and Western blotting.The localization and distribution of FLG were assessed using sinonasal mucosa.Results:A significant expression of FLG was detected at the mRNA and protein levels in HNECs.A moderate FLG immunoreactivity was observed in the epithelial cells,but no staining was seen in epithelial goblet cells.S100A7 increased the FLG mRNA level in HNECs in a dose-dependent manner and also up-regulated the FLG protein in a dose-dependent manner.Conclusion:This study significantly contributes to a better understanding of the role of FLG in the pathogenesis of airway inflammation from the viewpoint of the epithelial barrier function.FLG-related events in response to S100A7 protein may represent novel therapeutic targets for the treatment of upper airway inflammation.展开更多
为研究东阿阿胶对小鼠皮肤屏障损伤的修复作用。采用胶带剥离法构建小鼠皮肤屏障损伤模型,并使用阿胶对小鼠进行灌胃给药。造模后,每天检测小鼠受损皮肤处的经皮失水量(Transepidermal water loss,TEWL)。并于造模第4天和第7天后,通过...为研究东阿阿胶对小鼠皮肤屏障损伤的修复作用。采用胶带剥离法构建小鼠皮肤屏障损伤模型,并使用阿胶对小鼠进行灌胃给药。造模后,每天检测小鼠受损皮肤处的经皮失水量(Transepidermal water loss,TEWL)。并于造模第4天和第7天后,通过光学活体成像观察皮肤屏障损伤的修复效果。通过RT-qPCT检测丝聚蛋白(Filaggrin,FLG)、内披蛋白(Involucrin,IVL)、紧密连接蛋白闭锁小带蛋白1(Zonula occludens-1,ZO-1)与炎症因子白介素-1α(Interleukin-1α,IL-1α)、白介素-1β(Interleukin-1β,IL-1β)等的mRNA水平。通过免疫组化检测皮肤屏障相关蛋白的蛋白含量,免疫荧光检测胸腺基质淋巴生成素(Thymic stromal lymphopoietin,TSLP)的表达。结果显示,东阿阿胶显著降低胶带剥离小鼠的经皮失水量,降低皮肤厚度并改善表皮结构紊乱,上调FLG,IVL和ZO-1的mRNA相对表达量与蛋白表达,抑制TSLP的蛋白表达与炎症因子的mRNA相对表达量。结果表明,东阿阿胶通过调控屏障蛋白与炎症因子的表达实现皮肤屏障修复,为其在皮肤健康领域的应用提供理论依据。展开更多
Background： Atopic dermatitis （AD） is characterized by defective skin barrier and imbalance in T helper 1/T helper 2 （Th 1/Th2） cytokine expression.Filaggrin （FLG） is the key protein to maintaining skin barrier...Background： Atopic dermatitis （AD） is characterized by defective skin barrier and imbalance in T helper 1/T helper 2 （Th 1/Th2） cytokine expression.Filaggrin （FLG） is the key protein to maintaining skin barrier function.Recent studies indicated that Th1/Th2 cytokines influence FLG expression in keratinocytes.However, the role ofThl/Th2 cytokines on FLG processing is not substantially documented.Our aim was to investigate the impact ofThl/Th2 cytokines on FLG processing.Methods： HaCaT cells and normal human keratinocytes were cultured in low and high calcium media and stimulated by either interleukin （IL）-4, 13 or interferon-γ（IFN-γ）.FLG, its major processing proteases and key protease inhibitor lymphoepithelial Kazal-type-related inhibitor （LEKTI） were measured by both real-time quantitative polymerase chain reaction and Western blotting.Their expression was also evaluated in acute and chronic AD lesions by immunohistochemistry.Results： IL-4/13 significantly reduced, while IFN-γsignificantly up-regulated FLG expression.IL-4/13 significantly increased, whereas IFN-γsignificantly decreased the expression ofkallikreins 5 and 7, matriptase and channel-activating serine protease 1.On the contrary, IL-4/13 significantly decreased, while IFN-γincreased the expression of LEKTI and caspase-14.Similar trends were observed in AD lesions.Conclusions： Our results suggested that Th1/Th2 cytokines differentially regulated the expression of major FLG processing enzymes.The imbalance between Th1 and Th2 polarized immune response seems to extend to FLG homeostasis, through the network of FLG processing enzymes.展开更多
INTRODUCTION Atopic dermatitis （AD） is a common chronic inflammatory skin disorder that is characterized by dry skin and disturbed skin barrier functions. Mutations in the filaggrin （FLG） gene, the gene coding pro...INTRODUCTION Atopic dermatitis （AD） is a common chronic inflammatory skin disorder that is characterized by dry skin and disturbed skin barrier functions. Mutations in the filaggrin （FLG） gene, the gene coding profilaggrin/filaggrin, have a great impact on the epidermal barrier function and are an important predisposing factor for AD. However, in both Europeans and Asians,展开更多
文摘Filaggrin (FLG) plays an important role in the epidermal barrier function, which identified in patients with ichthyosis vulgaris(IV).To study the genetics of FLG mutations in Southern Chinese patients with IV. We evaluated the influence of five mutations (3321 delA, 441delA, 1249 insG, E1795X and S3296X) in a cohort of 65 IV Chinese patients and in 100 control individuals using the Sequenom? MassARRAY? system. The null allele frequency of 3321delA was 52.31%(34/65). FLG mutation 441delA was only found in one IV patients. FLG mutations 1249insG, E1795X and S3296X were not found in these patients. These findings show that the mutation 3321delA represent the most frequent genetic cause in Southern Chinese IV patients. Our findings confirm and extend the knowledge of the influence of FLG mutations in IV.
基金funded by the National Natural Science Foundation of China (NSFC 81571995)Specialized Research Fund for the Doctoral Program of Higher Education,(20133706110001)the Natural Science Foundation of Shandong Province (ZR2015HM069)
文摘The relationship between the Filaggrin gene(FLG) rs2065955 polymorphism and susceptibility to Epstein-Barr virus(EBV)-associated gastric carcinoma(EBVa GC) and EBV-negative gastric carcinoma(EBVn GC) was investigated in Shandong Province,China.We detected the FLG rs2065955 genotype and allele distribution by using PCR and restriction fragment length polymorphism(RFLP) in 64 EBVa GC,82 EBVn GC,and 111 normal control samples.Immunohistochemistry was used to detect the level of FLG protein in 35 EBVa GC and 51 EBVn GC tumor tissues.Compared with normal controls,the genotype CC and allele C of FLG rs2065955 showed higher frequency in EBVa GC and EBVn GC.There was no significant difference between EBVa GC and EBVn GC in allele distribution of FLG rs2065955,but the genotype CC was found more frequently in EBVa GC than in EBVn GC.The risk of developing either EBVa GC or EBVn GC in genotype CC was higher than in other genotypes.Furthermore,genotype CC of FLG rs2065955 may contribute more to the risk of developing EBVa GC than EBVn GC.There was no significant difference in the expression level of FLG protein between EBVa GC and EBVn GC.In conclusion,the FLG rs2065955 polymorphism was significantly related to gastric carcinoma.Allele C of FLG rs2065955 could be a risk factor for EBVa GC or EBVn GC,while genotype CC of FLG rs2065955 was especially associated with EBVa GC.
文摘The epidermis represents an essential barrier versus a broad range of exogenous stimuli. To form a functional epidermis, keratinocytes express filaggrin which plays a vital role in atopic dermatitis. However the relationship between filaggrin and other skin diseases remains unknown. In our study we chose 5 different common skin diseases and analyzed the expression of filaggrin in the skin using immunohistochemistry. Imiquimod (IMQ)-induced mouse model was used for detecting the filaggrin level and barrier function. The results indicated that the expression of filaggrin is reduced in psoriasis compared to the other skin diseases. Furthermore in vivo study showed that the skin barrier is defected with a decreased expression of filaggrin in IMQ-induced psoriasis mouse model, which is accompanied with an increased level of IL-17/IL-23. In conclusion, the defective skin barrier is involved in the development of psoriasis in human and mice with a reduced expression of filaggrin which may be regulated by the increased level of IL-17/IL-23 in the skin.
文摘Objective:Filaggrin(FLG)is a protein expressed in the epidermis and involved in the maintenance of the epidermal barrier.However,the expression and localization of FLG in the upper airway remain controversial.The present study aimed to determine the significance of FLG and the effect of S100A7 on FLG expression in the upper respiratory mucosa.Methods:Human nasal epithelial cells(HNECs)were cultured and examined for FLG expression and S100A7 effects by real-time polymerase chain reaction and Western blotting.The localization and distribution of FLG were assessed using sinonasal mucosa.Results:A significant expression of FLG was detected at the mRNA and protein levels in HNECs.A moderate FLG immunoreactivity was observed in the epithelial cells,but no staining was seen in epithelial goblet cells.S100A7 increased the FLG mRNA level in HNECs in a dose-dependent manner and also up-regulated the FLG protein in a dose-dependent manner.Conclusion:This study significantly contributes to a better understanding of the role of FLG in the pathogenesis of airway inflammation from the viewpoint of the epithelial barrier function.FLG-related events in response to S100A7 protein may represent novel therapeutic targets for the treatment of upper airway inflammation.
文摘Background： Atopic dermatitis （AD） is characterized by defective skin barrier and imbalance in T helper 1/T helper 2 （Th 1/Th2） cytokine expression.Filaggrin （FLG） is the key protein to maintaining skin barrier function.Recent studies indicated that Th1/Th2 cytokines influence FLG expression in keratinocytes.However, the role ofThl/Th2 cytokines on FLG processing is not substantially documented.Our aim was to investigate the impact ofThl/Th2 cytokines on FLG processing.Methods： HaCaT cells and normal human keratinocytes were cultured in low and high calcium media and stimulated by either interleukin （IL）-4, 13 or interferon-γ（IFN-γ）.FLG, its major processing proteases and key protease inhibitor lymphoepithelial Kazal-type-related inhibitor （LEKTI） were measured by both real-time quantitative polymerase chain reaction and Western blotting.Their expression was also evaluated in acute and chronic AD lesions by immunohistochemistry.Results： IL-4/13 significantly reduced, while IFN-γsignificantly up-regulated FLG expression.IL-4/13 significantly increased, whereas IFN-γsignificantly decreased the expression ofkallikreins 5 and 7, matriptase and channel-activating serine protease 1.On the contrary, IL-4/13 significantly decreased, while IFN-γincreased the expression of LEKTI and caspase-14.Similar trends were observed in AD lesions.Conclusions： Our results suggested that Th1/Th2 cytokines differentially regulated the expression of major FLG processing enzymes.The imbalance between Th1 and Th2 polarized immune response seems to extend to FLG homeostasis, through the network of FLG processing enzymes.
文摘INTRODUCTION Atopic dermatitis （AD） is a common chronic inflammatory skin disorder that is characterized by dry skin and disturbed skin barrier functions. Mutations in the filaggrin （FLG） gene, the gene coding profilaggrin/filaggrin, have a great impact on the epidermal barrier function and are an important predisposing factor for AD. However, in both Europeans and Asians,
