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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.

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Immunofluorescence localization of FLG2 and FLG in human skin.Skin sections were stained with a mixture of anti-FLG2 and anti-FLG antibody. The images show FLG2-Alexa-Fluor as red while FLG-FITC as green. Nuclear staining was done using DAPI. Comparative localization of FLG2-Alexa-Fluor and FLG-FITC is shown in the merged image. Scale bars, 30 µm.
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pone-0005227-g006: Immunofluorescence localization of FLG2 and FLG in human skin.Skin sections were stained with a mixture of anti-FLG2 and anti-FLG antibody. The images show FLG2-Alexa-Fluor as red while FLG-FITC as green. Nuclear staining was done using DAPI. Comparative localization of FLG2-Alexa-Fluor and FLG-FITC is shown in the merged image. Scale bars, 30 µm.

Mentions: Sub-cellular localisation of FLG2 was further analyzed by immunoelectron microscopy. By using the LR-White resin-embedded samples of prefixed skin biopsy specimen from the knee, FLG2 labelling was observed in both, the granular and cornified cell layers (Fig. 5B-a and -b). FLG2 labels were dispersed diffusely throughout the cytoplasm in the SC, while in the SG, FLG2 was localized to irregularly-shaped keratohyalin granules of various sizes (Fig. 5B-c and -d). These data suggested that the localization of FLG2 is similar to that of filaggrin, as previously reported [45]. Therefore, the spatial localisation of FLG2 in comparison with that of filaggrin was further analysed by immunofluorescent staining and laser scanning confocal microscopy. As shown in Fig. 6, both FLG2 and FLG were mainly expressed in the granular layers of human skin. Although the merged image showed that they exhibit similar spatial distribution, only partial co-localization was observed.


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)

Immunofluorescence localization of FLG2 and FLG in human skin.Skin sections were stained with a mixture of anti-FLG2 and anti-FLG antibody. The images show FLG2-Alexa-Fluor as red while FLG-FITC as green. Nuclear staining was done using DAPI. Comparative localization of FLG2-Alexa-Fluor and FLG-FITC is shown in the merged image. Scale bars, 30 µm.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0005227-g006: Immunofluorescence localization of FLG2 and FLG in human skin.Skin sections were stained with a mixture of anti-FLG2 and anti-FLG antibody. The images show FLG2-Alexa-Fluor as red while FLG-FITC as green. Nuclear staining was done using DAPI. Comparative localization of FLG2-Alexa-Fluor and FLG-FITC is shown in the merged image. Scale bars, 30 µm.
Mentions: Sub-cellular localisation of FLG2 was further analyzed by immunoelectron microscopy. By using the LR-White resin-embedded samples of prefixed skin biopsy specimen from the knee, FLG2 labelling was observed in both, the granular and cornified cell layers (Fig. 5B-a and -b). FLG2 labels were dispersed diffusely throughout the cytoplasm in the SC, while in the SG, FLG2 was localized to irregularly-shaped keratohyalin granules of various sizes (Fig. 5B-c and -d). These data suggested that the localization of FLG2 is similar to that of filaggrin, as previously reported [45]. Therefore, the spatial localisation of FLG2 in comparison with that of filaggrin was further analysed by immunofluorescent staining and laser scanning confocal microscopy. As shown in Fig. 6, both FLG2 and FLG were mainly expressed in the granular layers of human skin. Although the merged image showed that they exhibit similar spatial distribution, only partial co-localization was observed.

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