Epidermal turnover and iron metabolism in senile lentigo.

Senile lentigo (SL) is a pigmentary disorder associated with disrupted epidermal turnover. Trace minerals in the skin are known to regulate keratinocyte proliferation and differentiation. To clarify the role of iron in SL, we compared the expression of molecules related to iron metabolism between SL lesion (lesion) and the surrounding normal skin (nonlesion). Our results revealed that proteins involved in iron uptake and utilization such as transferrin receptor 1, iron regulatory protein 1, mitoferrin 1, and divalent metal transporter 1 were expressed in the lower epidermis in the nonlesion, while expression of them was also observed in the upper epidermis in the lesion. Ferroportin (FPN), involved in iron export, was expressed in the upper epidermis in the nonlesion, but was only scarcely expressed in the upper epidermis in the lesion. Hepcidin, which promotes FPN degradation, was expressed in the lower epidermis in the nonlesion; however, its expression was also observed in the upper epidermis in the lesion. These changes in the expression of molecules involved in iron uptake/export/utilization might reflect the altered iron utilization state in SL, resulting in disruption of keratinocyte differentiation and disturbing epidermal turnover. Our results suggest that the metabolism of iron in keratinocytes in SL differs from that in the normal epidermis, and these changes could be associated with the abnormal epidermal turnover and decreased melanin excretion in SL.

Taurine accelerates the synthesis of ceramides and hyaluronic acid in cultured epidermis and dermal fibroblasts.

Taurine is a sulfur-containing amino acid derivative that can be found in the majority of mammalian tissues. Taurine is also present in the skin and is involved in maintaining skin homeostasis by exerting osmoregulatory and antioxidant effects. Previous studies have indicated that taurine treatment is effective against age-, ultraviolet- or detergent-induced skin dysfunction. To determine the mechanism responsible for the beneficial actions of taurine in the skin, the present study aimed to evaluate the effects of taurine on epidermal components (ceramides and filaggrin) and on the dermal extracellular matrix, in three-dimensionally (3D) cultured epidermis and dermal fibroblasts, respectively. These cells were cultured in the presence of 3-50 mM taurine, and cells or culture medium were collected for analysis. The effects of taurine on transepidermal water loss (TEWL) in the skin and the expression of inflammatory cytokines, including IL-1α, IL-1ß and IL-1 receptor antagonist, were investigated in acetone-treated 3D-cultured epidermis using a Tewameter and reverse transcription-quantitative PCR (RT-qPCR), respectively. The mRNA expression levels of MMP-1 and hyaluronic acid (HA) production were measured in skin dermal fibroblasts using RT-qPCR and ELISA, respectively. Taurine was found to suppress acetone-induced elevation in TEWL in 3D-cultured epidermis. Taurine also stimulated the mRNA expression of ceramide synthase 4 and filaggrin, a major structural protein in the stratum corneum, in 3D-cultured epidermis. In skin dermal fibroblasts, taurine inhibited the IL-1α-stimulated mRNA and protein expression of MMP-1. In addition, taurine treatment increased HA synthase-2 mRNA expression and in turn HA production. Results from the present study suggest that the protective effect of taurine on the skin is associated with the enhancement of epidermal barrier component expression and modulation of dermal extracellular matrix metabolism.

Protective effect of taurine on UVB-induced skin aging in hairless mice.

Taurine, a sulfur-containing amino acid derivative, exists at a high concentration in the skin and is considered to play an important role in maintaining moisture homeostasis. This study investigated the effects of oral taurine supplementation on epidermal moisture content and wrinkle formation, as well as skin taurine content, using ultraviolet B (UVB)-irradiated hairless mice. Wrinkles were induced by exposing hairless mice to UVB radiation (70-100 mJ/cm2). Taurine was dissolved in drinking water at a concentration of 0.3 or 3% (w/v) and given to the mice ad libitum for 2-10 weeks. Taurine was then extracted from the dorsal skin, and the skin taurine content was determined using high-performance liquid chromatography (HPLC). The wrinkles were evaluated using a wrinkle score and the quantitative wrinkle area ratio. The exposure of the mice to UVB radiation for 4 weeks resulted in a decreased moisture content and increased transepidermal water loss (TEWL) in the skin, while taurine supplementation suppressed these changes. Oral supplementation with taurine for 8 weeks ameliorated the development of UVB-induced wrinkle formation. Furthermore, oral taurine supplementation for 4 weeks decreased pre-stablished wrinkles in a dose-dependent manner. Although the UVB radiation reduced the epidermal taurine content, oral taurine supplementation partly restored the taurine content in the epidermis. The present study showed that oral taurine supplementation is able to suppress UVB-induced wrinkle formation, which may be associated with the regulation of moisture content in the epidermis. The beneficial effects of taurine on skin aging may be attributed to its osmoregulatory role.

Age-related decline in the taurine content of the skin in rodents.

Taurine, a sulfur-containing amino acid, occurs at high concentrations in the skin, and plays a role in maintaining the homeostasis of the skin. We investigated the effects of aging on the content and localization of taurine in the skin of mice and rats. Taurine was extracted from the skin samples of hairless mice and Sprague Dawley rats, and the taurine content of the skin was determined by high-performance liquid chromatography (HPLC). The results of the investigation revealed that the taurine content in both the dermis and epidermis of hairless mice declined significantly with age. Similar age-related decline in the skin taurine content was also observed in rats. In contrast, the taurine content in the sole remained unchanged with age. An immunohistochemical analysis also revealed a decreased skin taurine content in aged animals compared with younger animals, although no significant differences in the localization of taurine were observed between the two age groups. Supplementation of the drinking water of aged mice with 3% (w/v) taurine for 4 weeks increased the taurine content of the epidermis, but not the dermis. The present study showed for the first time that the taurine content of the skin decreased with age in mice and rats, which may be related to the impairment of the skin homeostasis observed with aging. The decreased taurine content of the epidermis in aged animals was able to be rescued by taurine supplementation.

Age-related changes of p75 neurotrophin receptor-positive adipose-derived stem cells.

BACKGROUND: The existence of multipotent stem cells in subcutaneous adipose tissue has been reported. We previously confirmed that p75 neurotrophin receptor (p75NTR; CD271)-positive cells in subcutaneous adipose tissue possessed multipotency, although changes of the characteristics in p75NTR-positive adipose-derived stem cells (ASCs) with aging remain unclear. OBJECTIVE: To investigate the effect of aging on p75NTR-positive ASCs. METHODS: The number of p75NTR-positive ASCs in subcutaneous adipose tissue of ICR mice aged 3-24 weeks was analyzed by immunostaining and flow cytometry. Subsequently, the cells were isolated and their ability to attach to the cell culture dish, proliferation rate (doubling time) and the expression of senescence-associated beta-galactosidase (SA-beta gal), a cellular senescence marker, were assessed. Age-related changes in the differentiation potential of p75NTR-positive cells in adipogenic, osteogenic, chondrogenic and myogenic lineage were also investigated. RESULTS: The number of ASCs per unit of tissue weight in adipose tissue and the attachment rate of isolated cells decreased with aging. No difference in the cell proliferation rate and the percentage of SA-beta gal-positive cells was detected. Although the efficacy of differentiation into adipogenic and osteogenic lineages slightly decreased with aging, the differentiation potential into chondrogenic and myogenic lineages was not changed. CONCLUSION: The number of ASCs per unit of tissue weight decreased in aged mice. However, the cells possessed proliferation and differentiation potentials almost equal to those of young mice even though the differentiation potentials showed a tendency of decrease. These results raise the possibility that stem cell functions, self-renewal and multipotency, are maintained regardless of aging.

A peptide derived from tenascin-C induces beta1 integrin activation through syndecan-4.

Tenascin-C (TN-C) is unique for its cell adhesion modulatory function. We have shown that TNIIIA2, a synthetic 22-mer peptide derived from TN-C, stimulated beta1 integrin-mediated cell adhesion of nonadherent and adherent cell types, by inducing activation of beta1 integrin. The active site of TNIIIA2 appeared cryptic in the TN-C molecule but was exposed by MMP-2 processing of TN-C. The following results suggest that cell surface heparan sulfate (HS) proteoglycan (HSPG), including syndecan-4, participated in TNIIIA2-induced beta1 integrin activation: 1) TNIIIA2 bound to cell surface HSPG via its HS chains, as examined by photoaffinity labeling; 2) heparitinase I treatment of cells abrogated beta1 integrin activation induced by TNIIIA2; 3) syndecan-4 was isolated by affinity chromatography using TNIIIA2-immobilized beads; 4) small interfering RNA-based down-regulation of syndecan-4 expression reduced TNIIIA2-induced beta1 integrin activation, and consequent cell adhesion to fibronectin; 5) overexpression of syndecan-4 core protein enhanced TNIIIA2-induced activation of beta1 integrin. However, treatments that targeted the cytoplasmic region of syndecan-4, including ectopic expression of its mutant truncated with the cytoplasmic domains and treatment with protein kinase Calpha inhibitor Gö6976, did not influence the TNIIIA2 activity. These results suggest that a TNIIIA2-related matricryptic site of the TN-C molecule, exposed by MMP-2 processing, may have bound to syndecan-4 via its HS chains and then induced conformational change in beta1 integrin necessary for its functional activation. A lateral interaction of beta1 integrin with the extracellular region of the syndecan-4 molecule may be involved in this conformation change.