High impact information on Flg

• At the same time the expression of the early differentiation marker keratin 10 was inhibited, whereas filaggrin expression and epidermal permeability were less affected [1].
• Analysis of tryptic peptides of filaggrin defined a 26-residue linker segment when aligned on the amino acid sequence of one repeat unit of mouse profilaggrin deduced from a cDNA sequence (Rothnagel, J. A., Mehrel, T., Idler, W. W., Roop, D. R., and Steinert, P. M. (1987) J. Biol. Chem. 262, 15643-15648) [2].
• The expression of keratin 10 and the maturation of filaggrin were inhibited, and epidermal permeability barrier became less efficient, indicating compromised terminal differentiation by epidermal growth factor [3].
• Furthermore, filaggrin and loricrin mRNA levels, and filaggrin, loricrin, and involucrin protein levels all increased with air exposure [4].
• Additionally, protein and mRNA levels of loricrin and filaggrin, two structural proteins of stratum corneum, were increased in treated epidermis, as were the activities of two lipid catabolic enzymes critical to stratum corneum function, beta-glucocerebrosidase and steroid sulfatase [5].

Biological context of Flg

• Comparison of the rat filaggrin sequence with that of mouse and human filaggrin and with the sequence of phosphorylated peptides from mouse profilaggrin indicates that the proteins share extensive amino acid sequence similarities, especially in the two phosphorylated regions [6].
• Whereas profilaggrin/filaggrin and loricrin were not expressed at day 17 of gestation, by day 19 both were present in the upper layers of the epidermis and both became still more abundant by day 21 [7].

Anatomical context of Flg

• Exposure to 12-O-tetradecanoylphorbol-13-acetate (TPA) induces the synthesis of histidine-rich protein (filaggrin) in monolayer cultures of rat keratinocytes [8].
• AFA titers were estimated by immunoblotting on filaggrin enriched human epidermis extracts, and AKA titers by indirect immunofluorescence (IIF) on rat esophagus epithelium [9].

Associations of Flg with chemical compounds

• These high-molecular-weight filaggrin precursors can be rapidly labeled with histidine and extracted from the epidermis under denaturing conditions [10].
• Finally, occlusion with a water-impermeable membrane prevented both the air-exposure-induced increase in lipid enzyme activity, and the expression of loricrin, filaggrin, and involucrin [4].
• In contrast, dihydrotestosterone treatment delayed the expression of profilaggrin/filaggrin and loricrin [7].
• The size of filaggrin mRNA was estimated by sedimenting poly(A+) RNA through isokinetic sucrose gradients [11].
• Whereas neither profilaggrin/filaggrin nor loricrin were expressed in control explants cultured for 2 d, they were seen in explants treated with either thyroid hormone, glucocorticoids, or estrogens [7].

Other interactions of Flg

• 5. Cathepsin B degraded rat epidermal filaggrin into small fragments at pH 4.0 and 5.5., and was inhibited by a specific cysteine proteinase inhibitor, N-[N-(L-3-trans-carboxyoxirane-2-carbonyl)L-leucyl]- agmatin [12].
• Since the filaggrin linker segment peptide was efficiently conjugated with P-cystatin alpha and was mediated by epidermal TGase in the presence of Ca2+ ions, filaggrin is a candidate for the glutamine-rich linkage protein to conjugate with lysine-rich P-cystatin alpha [13].

Analytical, diagnostic and therapeutic context of Flg

• The distribution of filaggrin shown by immunofluorescence in the stratum corneum of the rat changed dramatically during the first hours of postnatal life [14].
• Immunoblotting studies have demonstrated that profilaggrin is synthesized in both cultured human keratinocytes and in a long-lived line of cultured rat keratinocytes, but only in the latter is the protein processed to a product of the molecular weight of filaggrin [15].
• Profilaggrin/filaggrin and loricrin expression, assessed by in situ hybridization and by immunohistochemistry, were progressively increased during epidermal ontogenesis [7].
• Immunoprecipitation of translated proteins with specific antibody against rat filaggrin revealed a diffuse radiolabeled band with a molecular weight of approximately 250 X 10(3) on SDS-polyacrylamide gels [11].
• A high performance liquid chromatography method to obtain rat epidermal filaggrin [16].

References