Language：English   Publisher：Journal of Dermatological Science  

Background: Age-related thinning and reduced cell proliferation in the human epidermis are associated with the accumulation of senescent cells and decreases in the number and function of epidermal stem cells. Objective: This study examined the expression of INHBA/Activin-A in human epidermis and expression differences with age, and the effect of Activin-A on epidermal stem/progenitor cells. Methods: Immunohistochemical staining was used to analyze age-related changes in the expression of INHBA/Activin-A in the epidermal tissue of young and old subjects. Epidermal INHBA/Activin-A expression levels, epidermal morphology, and the number of epidermal stem/progenitor cells or proliferating cells were investigated using older abdominal skin samples. The effects of Activin-A on the development of a three-dimensional (3D) reconstructed epidermis and cell proliferation were also assessed. Results: INHBA/Activin-A expression levels in the human epidermis increased with age, although they varied among individuals. In the epidermis of older abdominal skin samples, INHBA/Activin-A expression levels negatively correlated with epidermal thickness, the rete ridge depth and the interdigitation index. The proportion of epidermal stem/progenitor cells and proliferating cells decreased with increases in INHBA/Activin-A expression levels. Activin-A had no effect on the differentiation of keratinocytes in the 3D-reconstructed epidermis; however, thinning of the 3D epidermis was noted. Moreover, the addition of Activin-A inhibited the proliferation of epidermal stem/progenitor cells in a concentration-dependent manner. Conclusions: Age-related increased in INHBA/Activin-A expression levels were observed in the human epidermis, and may contribute to epidermal thinning and decreases in the number of epidermal stem/progenitor cells and proliferative activity.

DOI： 10.1016/j.jdermsci.2022.05.001

Web of Science

Scopus

PubMed

Language：English   Publisher：Experimental Dermatology  

The constitution and skin type of individuals are influenced by various factors. Recently, the influence of genetic predispositions on these has been emphasized. To date, genome-wide association studies (GWAS) have shown several single nucleotide polymorphisms (SNPs) that affect individual's constitution and skin type. However, these studies have mainly focused on the Caucasian population, and only a few association analyses with the constitution and skin type of individuals involving a Japanese population have been conducted. In this study, we conducted a GWAS analysis of 9 phenotypes regarding the constitution or skin type of 1108 Japanese women based on a questionnaire. As a result, in addition to SNPs known to be involved in phenotypes in the past, we discovered new SNPs and genetic regions related to darkness of pigmented spots, skin flushing, frequency of rough skin and responsiveness to cosmetics.

DOI： 10.1111/exd.14430

Web of Science

Scopus

PubMed

Language：English   Publisher：The Pharmaceutical Society of Japan  

<p>Currently, human-skin derived cell culture is a basic technique essential for dermatological research, cellular engineering research, drug development, and cosmetic development. But the number of donors is limited, and primary cell function reduces through cell passage. In particular, since adult stem cells are present in a small amount in living tissues, it has been difficult to obtain a large amount of stem cells and to stably culture them. In this study, skin derived cells were isolated from the epidermis, dermis, and adipose tissue collected from single donor, and immortalization was induced through gene transfer. Subsequently, cell lines that could be used as stem cell models were selected using the differentiation potential and the expression of stem cell markers as indices, and it was confirmed that these could be stably cultured. The immortalized cell lines established in this study have the potential to be applied not only to basic dermatological research but also to a wide range of fields such as drug screening and cell engineering.</p>

DOI： 10.1248/bpb.b21-00058

Web of Science

Scopus

PubMed

CiNii Research

Language：Japanese   Publisher：The Society of Cosmetic Chemists of Japan  

<p>IGF-1 (insulin-like growth factor-1) has multiple functions regarding cell proliferation and differentiation. In the skin, IGF-1 is known to have the promoting effect of keratinocyte proliferation, the accelerating effect of collagen production and the inhibitory effect of collagen degradation in fibroblasts. It is well known that the functional expression of IGF-1 declines as the production amount of IGF-1 decreases with aging, but the age-related change on the cells that receive IGF-1 has not been elucidated enough. In this study, we investigated the age-dependent change of IGF-1 function regulating ability in skin cells. The proliferation of aged keratinocytes was not promoted and the change of collagen metabolism in aged fibroblasts was not induced, even when IGF-1 was added to these cells. In addition, the expression level of IGFBP-4 (IGF binding protein-4), which has been reported to suppress the function of IGF-1, was significantly increased in both keratinocytes and fibroblasts with aging. Furthermore, when IGFBP-4 was added to these cells with IGF-1, the promoting effect of keratinocyte proliferation, the accelerating effect of collagen production and the inhibitory effect of collagen degradation in fibroblasts were suppressed. These results suggest that one of the causes of impaired expression of IGF-1 function with aging is a decrease of IGF-1 signaling due to age-dependent increase of IGFBP-4 in the cells that receive IGF-1.</p>

DOI： 10.5107/sccj.54.33

CiNii Research

Language：Japanese   Publisher：Japanese Cosmetic Science Society  

<p>Recently, it has become clear that Na⁺/H⁺ exchanger 1 (NHE1) plays an important role in the acidification of skin surface. NHE1 exists on the cell membrane of keratinocytes and regulates intracellular pH by effectively extruding H⁺ ions from intracellular compartments in exchange for external sodium ions, which also controls the acidification of extracellular microdomains and, consequently, was suggested to contributes to skin surface pH. Our previous study using human skin suggested that NHE1 protein amount, skin surface pH, and the onset of rough skin are related to each other. In this study, we investigated how NHE1 participated in skin surface pH, and the water holding capacity and the barrier function of the stratum corneum in human keratinocytes. A NHE1 activator significantly increased the mRNA expression of filaggrin (FLG) and serine palmitoyl transferase (SPT), a ceramide synthesis enzyme, while a NHE1 inhibitor significantly decreased the mRNA expression of both. Environmental and mental stress factors decreased the NHE1 mRNA expression in human keratinocytes. Moreover, a mild acidic environment significantly decreased the FLG and SPT mRNA expression in human keratinocytes. On the basis of these results, NHE1 was suggested to play an important role in not only controlling skin surface pH but also maintaining water holding capacity and barrier function of stratum corneum. Furthermore, decreased level of NHE1 due to environmental and mental stress was assumed to decrease water holding capacity and barrier function of stratum corneum, followed by the onset of rough skin. Therefore, to improve rough skin, preventing the depression of NHE1 function was considered to be more important than mere acidification of skin surface.</p>

DOI： 10.11469/koshohin.43.1

CiNii Research