Hyaluronan (hyaluronic acid, HA) is an abundant matrix component between keratinocytes of the epidermis in vivo, but its function there remains unclear. We used a lift culture model, in which rat epidermal keratinocytes (REKs) stratify at an air-liquid interface, to ask whether HA may regulate epidermal proliferation and/or differentiation. In this model, early markers of differentiation (keratin 10), and later markers (profilaggrin, keratohyalin granules, cornified layers) are faithfully expressed, both temporally and spatially. HA, measured using two different analytical techniques, accumulated to high levels only in the presence of an intact basement membrane that seals the epidermal compartment. To test whether HA has a functional role in differentiation, Streptomyces hyaluronidase (StrepH, 1 U/ml; digests >95% of HA within 4 h) was added daily to lift cultures during stratification time-course experiments over 5 days. In StrepH-treated cultures, the expression of profilaggrin and the number and size of keratohyalin granules were significantly increased relative to controls using semiquantitative histological analyses. The StrepH-related accumulation of K10 protein and profilaggrin/filaggrin were confirmed by Western analyses. Thus, it appears that the presence of intercellular HA in the epidermis acts as a brake upon intracellular events that occur during keratinocyte differentiation. 相似文献
Summary Sentence: Conditional ablation of AP-2γ results in a delay in skin development and abnormal expression of p63, K14, K1, filaggrin, repetin and secreted Ly6/Plaur domain containing 1, key genes required for epidermal development and differentiation.The development of the epidermis, a stratified squamous epithelium, is dependent on the regulated differentiation of keratinocytes. Differentiation begins with the initiation of stratification, a process tightly controlled through proper gene expression. AP-2γ is expressed in skin and previous research suggested a pathway where p63 gene induction results in increased expression of AP-2γ, which in turn is responsible for induction of K14. This study uses a conditional gene ablation model to further explore the role of AP-2γ in skin development. Mice deficient for AP-2γ exhibited delayed expression of p63, K14, and K1, key genes required for development and differentiation of the epidermis. In addition, microarray analysis of E16.5 skin revealed delayed expression of additional late epidermal differentiation genes: filaggrin, repetin and secreted Ly6/Plaur domain containing 1, in mutant mice. The genetic delay in skin development was further confirmed by a functional delay in the formation of an epidermal barrier. These results document an important role for AP-2γ in skin development, and reveal the existence of regulatory factors that can compensate for AP-2γ in its absence. 相似文献
The relationship between the Filaggrin gene (FLG) rs2065955 polymorphism and susceptibility to Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) and EBV-negative gastric carcinoma (EBVnGC) 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 EBVaGC, 82 EBVnGC, and 111 normal control samples. Immunohistochemistry was used to detect the level of FLG protein in 35 EBVaGC and 51 EBVnGC tumor tissues. Compared with normal controls, the genotype CC and allele C of FLG rs2065955 showed higher frequency in EBVaGC and EBVnGC. There was no significant difference between EBVaGC and EBVnGC in allele distribution of FLG rs2065955, but the genotype CC was found more frequently in EBVaGC than in EBVnGC. The risk of developing either EBVaGC or EBVnGC in genotype CC was higher than in other genotypes. Furthermore, genotype CC of FLG rs2065955 may contribute more to the risk of developing EBVaGC than EBVnGC. There was no significant difference in the expression level of FLG protein between EBVaGC and EBVnGC. In conclusion, the FLG rs2065955 polymorphism was significantly related to gastric carcinoma. Allele C of FLG rs2065955 could be a risk factor for EBVaGC or EBVnGC, while genotype CC of FLG rs2065955 was especially associated with EBVaGC.
