Limits...
Molecular identification and expression analysis of filaggrin-2, a member of the S100 fused-type protein family.

Wu Z, Hansmann B, Meyer-Hoffert U, Gläser R, Schröder JM - PLoS ONE (2009)

Bottom Line: We found that FLG2 transcripts are present in skin, thymus, tonsils, stomach, testis and placenta.We provide evidences that like filaggrin, FLG2 is initially expressed by upper granular cells, proteolytically processed and deposited in the stratum granulosum and stratum corneum (SC) layers of normal epidermis.Thus, FLG2 and filaggrin may have overlapping and perhaps synergistic roles in the formation of the epidermal barrier, protecting the skin from environmental insults and the escape of moisture by offering precursors of natural moisturizing factors.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, University Hospital of Schleswig-Holstein, Kiel, Germany.

ABSTRACT
Genes of the S100 fused-type protein (SFTP) family are clustered within the epidermal differentiation complex and encode essential components that maintain epithelial homeostasis and barrier functions. Recent genetic studies have shown that mutations within the gene encoding the SFTP filaggrin cause ichthyosis vulgaris and are major predisposing factors for atopic dermatitis. As a vital component of healthy skin, filaggrin is also a precursor of natural moisturizing factors. Here we present the discovery of a member of this family, designated as filaggrin-2 (FLG2) that is expressed in human skin. The FLG2 gene encodes a histidine- and glutamine-rich protein of approximately 248 kDa, which shares common structural features with other SFTP members, in particular filaggrin. We found that FLG2 transcripts are present in skin, thymus, tonsils, stomach, testis and placenta. In cultured primary keratinocytes, FLG2 mRNA expression displayed almost the same kinetics as that of filaggrin following Ca(2+) stimulation, suggesting an important role in molecular regulation of epidermal terminal differentiation. We provide evidences that like filaggrin, FLG2 is initially expressed by upper granular cells, proteolytically processed and deposited in the stratum granulosum and stratum corneum (SC) layers of normal epidermis. Thus, FLG2 and filaggrin may have overlapping and perhaps synergistic roles in the formation of the epidermal barrier, protecting the skin from environmental insults and the escape of moisture by offering precursors of natural moisturizing factors.

Show MeSH

Related in: MedlinePlus

Localization of filaggrin-2 in human epidermis.(A) Immunohistochemical analyses of FLG2 in human skin sections. Healthy skin sections from palmar (panel a; scale bar, 60 µm) and plantar (panel c; scale bar, 120 µm) sites as well as the upper leg region (panel b; scale bar, 60 µm) were stained with anti-FLG2 antibody. Specificity of antibody was confirmed by blocking the antibody with the antigen (panel d; scale bar, 60 µm). Representative experiments out of three are shown. (B) Post-embedding immunoelectron microscopy of FLG2 (10 nm gold) in healthy foreskin. FLG2 labels are present in both granular and cornified cells (panels a and b). Note that FLG2 labels are either diffusely dispersed in the cytoplasm (panel c) or grouped as keratohyalin granules (panel d). SG, stratum granulosum; SC, stratum corneum.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2668185&req=5

pone-0005227-g005: Localization of filaggrin-2 in human epidermis.(A) Immunohistochemical analyses of FLG2 in human skin sections. Healthy skin sections from palmar (panel a; scale bar, 60 µm) and plantar (panel c; scale bar, 120 µm) sites as well as the upper leg region (panel b; scale bar, 60 µm) were stained with anti-FLG2 antibody. Specificity of antibody was confirmed by blocking the antibody with the antigen (panel d; scale bar, 60 µm). Representative experiments out of three are shown. (B) Post-embedding immunoelectron microscopy of FLG2 (10 nm gold) in healthy foreskin. FLG2 labels are present in both granular and cornified cells (panels a and b). Note that FLG2 labels are either diffusely dispersed in the cytoplasm (panel c) or grouped as keratohyalin granules (panel d). SG, stratum granulosum; SC, stratum corneum.

Mentions: To evaluate the expression of the FLG2 protein, goat polyclonal antibodies against rFLG2-S were generated and used for analysis of FLG2 expression in healthy human tissues and cells. The FLG2-S peptide was used for immunization because it is located within the spacer region of FLG2 exhibiting the least sequence similarity to the other SFTP members. In immunohistochemical studies, the FLG2 immunoreactivity was detected weakly in the esophagus, tonsils and testis (Fig. S1), but strongly in the stratum granulosum (SG) and stratum corneum (SC) layers of human skin (Fig. 5A). All skin samples investigated exhibited the same staining pattern. Exemplarily, localizations of immunoreactive FLG2 in palmar (Fig. 5A-a) and plantar skin (Fig. 5A-c) as well as in the facial region (Fig. 5A-b) are shown. In scalp hair follicles, the FLG2 immunoreactivity was found to be mainly restricted within the granular and cornified cells surrounding the infundibular outer root sheath (ORS) though weak immunoreactivity was also present in central and proximal ORS (Fig. S1).


Molecular identification and expression analysis of filaggrin-2, a member of the S100 fused-type protein family.

Wu Z, Hansmann B, Meyer-Hoffert U, Gläser R, Schröder JM - PLoS ONE (2009)

Localization of filaggrin-2 in human epidermis.(A) Immunohistochemical analyses of FLG2 in human skin sections. Healthy skin sections from palmar (panel a; scale bar, 60 µm) and plantar (panel c; scale bar, 120 µm) sites as well as the upper leg region (panel b; scale bar, 60 µm) were stained with anti-FLG2 antibody. Specificity of antibody was confirmed by blocking the antibody with the antigen (panel d; scale bar, 60 µm). Representative experiments out of three are shown. (B) Post-embedding immunoelectron microscopy of FLG2 (10 nm gold) in healthy foreskin. FLG2 labels are present in both granular and cornified cells (panels a and b). Note that FLG2 labels are either diffusely dispersed in the cytoplasm (panel c) or grouped as keratohyalin granules (panel d). SG, stratum granulosum; SC, stratum corneum.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2668185&req=5

pone-0005227-g005: Localization of filaggrin-2 in human epidermis.(A) Immunohistochemical analyses of FLG2 in human skin sections. Healthy skin sections from palmar (panel a; scale bar, 60 µm) and plantar (panel c; scale bar, 120 µm) sites as well as the upper leg region (panel b; scale bar, 60 µm) were stained with anti-FLG2 antibody. Specificity of antibody was confirmed by blocking the antibody with the antigen (panel d; scale bar, 60 µm). Representative experiments out of three are shown. (B) Post-embedding immunoelectron microscopy of FLG2 (10 nm gold) in healthy foreskin. FLG2 labels are present in both granular and cornified cells (panels a and b). Note that FLG2 labels are either diffusely dispersed in the cytoplasm (panel c) or grouped as keratohyalin granules (panel d). SG, stratum granulosum; SC, stratum corneum.
Mentions: To evaluate the expression of the FLG2 protein, goat polyclonal antibodies against rFLG2-S were generated and used for analysis of FLG2 expression in healthy human tissues and cells. The FLG2-S peptide was used for immunization because it is located within the spacer region of FLG2 exhibiting the least sequence similarity to the other SFTP members. In immunohistochemical studies, the FLG2 immunoreactivity was detected weakly in the esophagus, tonsils and testis (Fig. S1), but strongly in the stratum granulosum (SG) and stratum corneum (SC) layers of human skin (Fig. 5A). All skin samples investigated exhibited the same staining pattern. Exemplarily, localizations of immunoreactive FLG2 in palmar (Fig. 5A-a) and plantar skin (Fig. 5A-c) as well as in the facial region (Fig. 5A-b) are shown. In scalp hair follicles, the FLG2 immunoreactivity was found to be mainly restricted within the granular and cornified cells surrounding the infundibular outer root sheath (ORS) though weak immunoreactivity was also present in central and proximal ORS (Fig. S1).

Bottom Line: We found that FLG2 transcripts are present in skin, thymus, tonsils, stomach, testis and placenta.We provide evidences that like filaggrin, FLG2 is initially expressed by upper granular cells, proteolytically processed and deposited in the stratum granulosum and stratum corneum (SC) layers of normal epidermis.Thus, FLG2 and filaggrin may have overlapping and perhaps synergistic roles in the formation of the epidermal barrier, protecting the skin from environmental insults and the escape of moisture by offering precursors of natural moisturizing factors.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, University Hospital of Schleswig-Holstein, Kiel, Germany.

ABSTRACT
Genes of the S100 fused-type protein (SFTP) family are clustered within the epidermal differentiation complex and encode essential components that maintain epithelial homeostasis and barrier functions. Recent genetic studies have shown that mutations within the gene encoding the SFTP filaggrin cause ichthyosis vulgaris and are major predisposing factors for atopic dermatitis. As a vital component of healthy skin, filaggrin is also a precursor of natural moisturizing factors. Here we present the discovery of a member of this family, designated as filaggrin-2 (FLG2) that is expressed in human skin. The FLG2 gene encodes a histidine- and glutamine-rich protein of approximately 248 kDa, which shares common structural features with other SFTP members, in particular filaggrin. We found that FLG2 transcripts are present in skin, thymus, tonsils, stomach, testis and placenta. In cultured primary keratinocytes, FLG2 mRNA expression displayed almost the same kinetics as that of filaggrin following Ca(2+) stimulation, suggesting an important role in molecular regulation of epidermal terminal differentiation. We provide evidences that like filaggrin, FLG2 is initially expressed by upper granular cells, proteolytically processed and deposited in the stratum granulosum and stratum corneum (SC) layers of normal epidermis. Thus, FLG2 and filaggrin may have overlapping and perhaps synergistic roles in the formation of the epidermal barrier, protecting the skin from environmental insults and the escape of moisture by offering precursors of natural moisturizing factors.

Show MeSH
Related in: MedlinePlus