Biomedical subjects

Kyu Han Kim

Publications and source records attributed to Kyu Han Kim.

At least 19 recordsLinked to original sources

PubMed2007

Expression of androgen and estrogen receptors in human scalp mesenchymal cells in vitro.

The expression levels of sex hormone receptors were identified to be different in human mesenchymal cells [dermal papilla cell (DPC), dermal sheath cell (DSC), dermal fibroblast and (DF)] from occipital scalps. Transcriptional and translational activities of androgen receptor (AR) and estrogen receptor beta (ERbeta) were most intensely expressed in DPC, followed by DSC and DF. On the contrary, estrogen receptor alpha (ERalpha) was shown with the strongest positivity in DSC, succeeded by DPC and DF subsequently. Immunocytochemical staining showed the similar expression to previous patterns. Our results suggest that the expression levels of ER subtypes and AR may be important for the regulation of follicular mesenchymal cells in human scalp. Further studies of the interactions of hormones and receptors in human hair follicles are required to promote our understanding of the effects of sex hormones on hair biology.

Adult↗

PubMed2007

The additive effects of minoxidil and retinol on human hair growth in vitro.

Minoxidil enhances hair growth by prolonging the anagen phase and induces new hair growth in androgenetic alopecia (AGA), whereas retinol significantly improves scalp skin condition and promotes hair growth. We investigated the combined effects of minoxidil and retinol on human hair growth in vitro and on cultured human dermal papilla cells (DPCs) and epidermal keratinocytes (HaCaT). The combination of minoxidil and retinol additively promoted hair growth in hair follicle organ cultures. In addition, minoxidil plus retinol more effectively elevated phosphorylated Erk, phosphorylated Akt levels, and the Bcl-2/Bax ratio than minoxidil alone in DPCs and HaCaT. We found that the significant hair shaft elongation demonstrated after minoxidil plus retinol treatment would depend on the dual kinetics associated with the activations of Erk- and Akt-dependent pathways and the prevention of apoptosis by increasing the Bcl-2/Bax ratio.

Adult↗

PubMed2006

Suppression of spontaneous dermatitis in NC/Nga murine model by PG102 isolated from Actinidia arguta.

Atopic dermatitis (AD) is a chronic inflammatory skin disease, which requires safe and effective pharmacological therapy. We previously found that two preparations from Actinidia arguta, PG102T, and PG102E, could modulate Th1/Th2 pathways and suppress IgE biosynthesis. This study was performed to assess the therapeutic effects of PG102T and PG102E on the development of dermatitis in NC/Nga mice, characterized by the spontaneous onset of AD along with an elevated level of IgE under conventional conditions. PG102T or PG102E administration significantly reduced dermatitis severity as well as scratching tendency in conventional mice. The suppression of dermatitis by PG102 was accompanied by a decrease in the plasma level of IgE, IgG1, and IL-4 and also by an increase in that of IgG2a and IL-12. The splenic level of IL-4, IL-5, and IL-10 was downregulated, whereas that of IFN-gamma and IL-12 was increased. The number of eosinophils and the expression of eotaxin and thymus and activation-regulated chemokine were decreased by PG102T or PG102E. Histological findings also indicated that the thickening of epidermis/dermis and the dermal infiltration of inflammatory cells including mast cells were greatly inhibited. These data suggest that PG102 may be effective therapeutic agents for the treatment of AD.

Actinidia↗

PubMed2006

Photoprotective and anti-skin-aging effects of eicosapentaenoic acid in human skin in vivo.

Skin aging can be attributed to photoaging (extrinsic) and chronological (intrinsic) aging. Photoaging and intrinsic aging are induced by damage to human skin attributable to repeated exposure to ultraviolet (UV) irradiation and to the passage of time, respectively. In our previous report, eicosapentaenoic acid (EPA) was found to inhibit UV-induced matrix metalloproteinase-1 (MMP-1) expression in human dermal fibroblasts. Therefore, we investigated the effects of EPA on UV-induced skin damage and intrinsic aging by applying EPA topically to young and aged human skin, respectively. By immunohistochemical analysis and Western blotting, we found that topical application of EPA reduced UV-induced epidermal thickening and inhibited collagen decrease induced by UV light. It was also found that EPA attenuated UV-induced MMP-1 and MMP-9 expression by inhibiting UV-induced c-Jun phosphorylation, which is closely related to UV-induced activator protein-1 activation, and by inhibiting JNK and p38 activation. EPA also inhibited UV-induced cyclooxygenase-2 (COX-2) expression without altering COX-1 expression. Moreover, it was found that EPA increased collagen and elastic fibers (tropoelastin and fibrillin-1) expression by increasing transformin growth factor-beta expression in aged human skin. Together, these results demonstrate that topical EPA has potential as an anti-skin-aging agent.

Adult↗

PubMed2006

Non-invasive evaluation of hair interior morphology by X-ray microscope.

Lots of trials have been performed to obtain better microscopic images of hair structure. Although scanning electron microscopy (SEM) and transmission electron microscopy (TEM) provide detailed images of hair, artificial processing may modify the original images during sample preparation. To overcome this limitation, we applied newly-developed X-ray microscopy with an 80-100 nm spatial resolution to produce a detailed view of the morphological change of hair interior. This X-ray microscopy permits us to penetrate a hair shaft without any artificial change and also provides precise images of hair interior with fine resolution. We evaluated the interior morphological change of Japanese standard hair tress No. 8 by various treatments such as ultraviolet (UV) irradiation, heating, hair dyeing, decolorizing bleaching agents and permanent waving. Internal morphological images were relatively similar in both heated and UV-irradiated hair. They revealed coarsening of cuticles and dehydration of cortex and medulla. When compared with TEM, X-ray microscopy provides more intact images in the cuticle and may be a useful tool in observing fine cracks of hair cortex. Additionally, X-ray images were intact and not influenced by any processing procedures. In observing the external and internal structure of hair, its resolution seems to be somewhat lesser than TEM and there are also several remaining weaknesses to be improved. Hopefully, forthcoming technology will solve these problems in the near future.

Hair↗

PubMed2006

Perifollicular fibrosis: pathogenetic role in androgenetic alopecia.

Androgenetic alopecia (AGA) is a dihydrotestosterone (DHT)-mediated process, characterized by continuous miniaturization of androgen reactive hair follicles and accompanied by perifollicular fibrosis of follicular units in histological examination. Testosterone (T: 10(-9)-10(-7) M) treatment increased the expression of type I procollagen at mRNA and protein level. Pretreatment of finasteride (10(-8) M) inhibited the T-induced type I procollagen expression at mRNA (40.2%) and protein levels (24.9%). T treatment increased the expression of transforming growth factor-beta 1 (TGF-beta1) at protein levels by 81.9% in the human scalp dermal fibroblasts (DFs). Pretreatment of finasteride decreased the expression of TGF-beta1 protein induced by an average of T (30.4%). The type I procollagen expression after pretreatment of neutralizing TGF-beta1 antibody (10 microg/ml) was inhibited by an average of 54.3%. Our findings suggest that T-induced TGF-beta1 and type I procollagen expression may contribute to the development of perifollicular fibrosis in the AGA, and the inhibitory effects on T-induced procollagen and TGF-beta1 expression may explain another possible mechanism how finasteride works in AGA.

Alopecia↗

PubMed2006

Role of staphylococcal superantigen in atopic dermatitis: influence on keratinocytes.

Staphylococcus aureus may perform an crucial function in atopic dermatitis (AD), via the secretion of superantigens, including staphylococcal enterotoxins (SE) A or B, and toxic shock syndrome toxin-1 (TSST-1). Dysregulated cytokine production by keratinocytes (KCs) upon exposure to staphylococcal superantigens (SsAgs) may be principally involved in the pathophysiology of AD. We hypothesized that lesional KCs from AD may react differently to SsAgs compared to nonlesional skin or normal skin from nonatopics. We conducted a comparison of HLA-DR or CD1a expression in lesional skin as opposed to that in nonlesional or normal skin by immunohistochemistry (IHC). We also compared, using ELISA, the levels of IL-1alpha, IL-1beta, and TNF-alpha secreted by cultured KCs from lesional, nonlesional, and normal skin, after the addition of SEA, SEB and TSST-1. IHC revealed that both HLA-DR and CD1a expression increased significantly in the epidermis of lesional skin versus nonlesional or normal skin in quite a similar manner. IL-1alpha, IL-1beta, and TNF-alpha secretion was also significantly elevated in the cultured KCs from lesional skin after the addition of SsAgs. Our results indicated that KCs from lesional skin appear to react differently to SsAgs and increased proinflammatory cytokine production in response to SsAgs may contribute to the pathogenesis of AD.

Adult↗

PubMed2006

Incontinentia pigmenti: clinical observation of 40 Korean cases.

Incontinentia pigmenti (IP) is an uncommon genodermatosis that usually occurs in female infants. It is characterized by ectodermal, mesodermal, neurological, ocular, and dental manifestations. The aim of this study was to clarify clinical symptoms, accompanying diseases, and complications of IP. Forty cases of IP have been reviewed by their medical records, laboratory data, clinical photographs, and telephone survey. Male-to-female ratio was 1 to 19 and their onsets were mostly in utero. They were usually diagnosed during the neonatal period owing to their early expression of skin manifestation. Central nervous system anomalies were found in 46.7%. Ocular disorders and dental defects were detected in 66.7% and 72.7% respectively. The most commonly diagnosed anomalies were hypodontia, retinopathy, and seizure. For better understanding of IP, long term and close cooperation between dermatologists, pediatricians, neuroscientists, genetic counselors, and even dentists is crucial.

Central Nervous System Diseases↗

PubMed2005

Human hair growth ex vivo is correlated with in vivo hair growth: selective categorization of hair follicles for more reliable hair follicle organ culture.

Of the numerous assays used to assess hair growth, hair follicle organ culture model is one of the most popular and powerful in vitro systems. Changes in hair growth are commonly employed as a measurement of follicular activity. Hair cycle stage of mouse vibrissa follicles in vivo is known to determine subsequent hair growth and follicle behavior in vitro and it is recommended that follicles be taken at precisely the same cyclic stage. This study was performed to evaluate whether categorization of human hair follicles by the growth in vivo could be used to select follicles of the defined anagen stage for more consistent culture. Occipital scalp samples were obtained from three subjects, 2 weeks later after hair bleaching. Hair growth and follicle length of isolated anagen VI follicles were measured under a videomicroscope. Follicles were categorized into four groups according to hair growth and some were cultured ex vivo for 6 days. Follicles showed considerable variations with respect to hair growth and follicle length; however, these two variables were relatively well correlated. Hair growth in culture was closely related with hair growth rate in vivo. Moreover, minoxidil uniquely demonstrated a significant increase of hair growth in categorized hair follicles assumed at a similar early anagen VI stage of hair cycle. Selection of follicles at a defined stage based on hair-growth rate would permit a more reliable outcome in human hair follicle organ culture.

Adult↗

PubMed2005

Eicosapentaenoic acid inhibits UV-induced MMP-1 expression in human dermal fibroblasts.

Ultraviolet (UV) irradiation regulates UV-responsive genes, including matrix metalloproteinases (MMPs). Moreover, UV-induced MMPs cause connective tissue damage and the skin to become wrinkled and aged. Here, we investigated the effect of eicosapentaenoic acid (EPA), a dietary omega-3 fatty acid, on UV-induced MMP-1 expression in human dermal fibroblasts (HDFs). We found that UV radiation increases MMP-1 expression and that this is mediated by p44 and p42 MAP kinase (ERK) and Jun-N-terminal kinase (JNK) activation but not by p38 activation. Pretreatment of HDFs with EPA inhibited UV-induced MMP-1 expression in a dose-dependent manner and also inhibited the UV-induced activation of ERK and JNK by inhibiting ERK kinase (MEK1) and SAPK/ERK kinase 1 (SEK1) activation, respectively. Moreover, inhibition of ERK and JNK by EPA resulted in the decrease of c-Fos expression and c-Jun phosphorylation/expression induced by UV, respectively, which led to the inhibition of UV-induced activator protein-1 DNA binding activity. This inhibitory effect of EPA on MMP-1 was not mediated by an antioxidant effect. We also found that EPA inhibited 12-O-tetradecanoylphorbol-13-acetate- or tumor necrosis factor-alpha-induced MMP-1 expression in HDFs and UV-induced MMP-1 expression in HaCaT cells. In conclusion, our results demonstrate that EPA can inhibit UV-induced MMP-1 expression by inhibiting the MEK1/ERK/c-Fos and SEK1/JNK/c-Jun pathways. Therefore, EPA is a potential agent for the prevention and treatment of skin aging.

Cells, Cultured↗

PubMed2005

The effect of tiarellic acid on the expressions of matrix metalloproteinase-1 and type 1 procollagen in ultraviolet irradiated cultured human skin fibroblasts.

Long term and repeated exposure of ultraviolet (UV) light, a harmful environmental stress, on the skin often induces chronic skin diseases such as skin cancer as well as photoaging (premature skin aging), and the mechanisms of these skin damages are closely associated with up-regulation of matrix metalloproteinases (MMPs) activities. Here we investigated the effect of tiarellic acid on the expressions of MMP-1 and type 1 procollagen in ultraviolet irradiation of cultured human skin fibroblasts. Tiarellic acid reduced the expression of MMP-1 and induced the expression of type 1- procollagen at the protein levels in a dose-dependent manner by ultraviolet irradiation. Taken together, our results suggest that tiarellic acid plays an important role in the reduction of MMP-1 and induction of type 1- procollagen by ultraviolet irradiation.

Catechin↗

PubMed2005

Increased expression of 14-3-3varepsilon protein in intrinsically aged and photoaged human skin in vivo.

Skin aging is a complicated process associated with the passage of time and environmental exposure, especially to UV light. This aging phenomenon is related to alterations in various cellular mechanisms, such as changes in apoptosis, perturbations to cellular signaling, and an increased genetic instability. In this study, we investigated changes of proteins involved in intrinsic aging by the proteomic analysis of human sun-protected (upper inner arm) young and aged dermis. One of the proteins upregulated in aged dermis was identified as 14-3-3epsilon. This protein is an isoform of 14-3-3 protein, which is involved in cellular processes like signal transduction, cell cycle arrest, and apoptosis. 14-3-3epsilon is consistently found to be upregulated in the sun-protected dermis of aged skin, by Western blotting and immunohistochemical staining. In addition, we demonstrate that the expression of 14-3-3epsilon is further upregulated in the sun-exposed (photodamaged) dermis, and that the UV irradiation of young skin significantly upregulates 14-3-3epsilon in vivo. Our results suggest the possibility that the cellular processes related to 14-3-3epsilon protein play an important role in the photoaging and intrinsic aging of human skin.

14-3-3 Proteins↗

PubMed2005

Evaluation of the anti-inflammatory and atopic dermatitis-mitigating effects of BSASM, a multicompound preparation.

For effective management of atopic dermatitis (AD), it is important to introduce a therapeutic agent, which although having the fewest side effects, has the greatest anti-inflammatory effect. In the course of screening anti-inflammatory agents, we obtained BSASM, a mixture of several plant extracts. This study was designed to investigate the AD-mitigating effect of BSASM in patients, as well as its anti-inflammatory and immunomodulatory effects in an in vitro experiment. The anti-inflammatory effects of BSASM were evaluated by the level of production of proinflammatory cytokines. Clinical evaluation was also done using eczema area severity index (EASI) score in AD patients. BSASM inhibited LPS-induced activation of NF-kappaB promoter. In addition, LPS-induced an increase of IL-8, and the TNF-alpha production in THP-1 cells was also inhibited. These results suggest that BSASM has an anti-inflammatory activity. A clinical study in patients with AD showed that BSASM induced a reduction of EASI score, degree of pruritus, and TEWL on both the antecubital fossa and abdomen. Besides, BSASM had no irritative or allergic effects. Based on these results, we conclude that BSASM has anti-inflammatory and AD-mitigating effects.

Adjuvants, Immunologic↗

PubMed2005

Augmentation of UV-induced skin wrinkling by infrared irradiation in hairless mice.

Skin aging can be divided into intrinsic aging and photoaging. Sunlight is a major cause of photoaging, and is composed of ultraviolet (UV) and infrared (IR) radiation. Although the effects of UV radiation on skin aging have been widely studied, little is known about the biological effects of IR on the photoaging process in human skin. We found that chronic IR treatment induced wrinkles in hairless mice, and augments UV-induced wrinkle formation and UV-induced skin thickening in hairless mice. Histologically, we found that IR treatment augments UV-induced epidermal and dermal thickening, and that UV-induced increases of collagen and elastic fibers in dermis. Moreover, chronic IR treatment increased MMP-3 and MMP-13 mRNA expressions significantly in hairless mouse skin and augmented UV-induced MMP-3 and MMP-13 mRNA expressions and UV-induced MMP-2 and MMP-9 activities. From these results, we demonstrate that IR alone induces skin wrinkling and augments UV-induced wrinkle formation. Taken together, we suggest that IR plays an important role in the development of photoaging.

Animals↗

PubMed2005

Heat modulation of tropoelastin, fibrillin-1, and matrix metalloproteinase-12 in human skin in vivo.

Photoaged skin contains elastotic materials in the upper reticular dermis. This phenomenon is commonly known as solar elastosis. In this study, we investigated the effects of heat on the expression of tropoelastin and fibrillin-1, two main components of elastic fibers, and on matrix metalloproteinase (MMP)-12, the most active MMP against elastin, in human skin in vivo. Heat was found to increase tropoelastin mRNA and protein expression in the epidermis and in the dermis. Fibrillin-1 mRNA and protein expression were increased by heat in the epidermis, but were decreased in the dermis. We found that pre-treatment of skin with N-acetyl cysteine or genistein for 24 h prior to heat treatment inhibited the heat-induced expression of tropoelastin, but not of fibrillin-1. These data indicate that reactive oxygen species may play a role in tropoelastin expression by heat, but not in fibrillin-1 expression. We also found that heat treatment increases MMP-12 mRNA and protein expression in human skin. Our results suggest that the abnormal production of tropoelastin and fibrillin by heat in human skin and that their degradation by various MMP, such as MMP-12, may contribute to the accumulation of elastotic material in photoaged skin.

Acetylcysteine↗

PubMed2005

Modulation of collagen metabolism by the topical application of dehydroepiandrosterone to human skin.

Dehydroepiandrosterone (DHEA) and its sulfate conjugate (DHEA-S) are the most abundantly produced human adrenal steroids to be reduced with age. DHEA may be related to the process of skin aging through the regulation and degradation of extracelluar matrix protein. In this study, we demonstrate that DHEA can increase procollagen synthesis and inhibit collagen degradation by decreasing matrix metalloproteinases (MMP)-1 synthesis and increasing tisuue inhibitor of matrix metalloprotease (TIMP-1) production in cultured dermal fibroblasts. DHEA was found to inhibit ultraviolet (UV)-induced MMP-1 production and the UV-induced decrease of procollagen synthesis, probably due to the inhibition of UV-induced AP-1 activity. DHEA (5%) in ethanol:olive oil (1:2) was topically applied to buttock skin of volunteers 12 times over 4 weeks, and was found to significantly increase the expression of procollagen alpha1(I) mRNA and protein in both aged and young skin. On the other hand, topical DHEA significantly decreased the basal expression of MMP-1 mRNA and protein, but increased the expression of TIMP-1 protein in aged skin. We also found that DHEA induced the expressions of transforming growth factor-beta1 and connective tissue growth factor mRNA in cultured fibroblasts and aged skin, which may play a role in the DHEA-induced changes of procollagen and MMP-1 expression. Our results suggest the possibility of using DHEA as an anti-skin aging agent.

Adjuvants, Immunologic↗

PubMed2005

H2O2 accumulation by catalase reduction changes MAP kinase signaling in aged human skin in vivo.

To understand the molecular alterations occurring during the aging process, we compared mitogen-activated protein (MAP) kinase activities in the intrinsically aged and photoaged skins in the same individuals. Furthermore, we investigated the molecular events related to MAP kinase changes in intrinsically aged and photoaged skins. We found that extracellular-signal-regulated kinase (ERK) activity in photoaged skin was reduced, and that the activities of c-Jun N-terminal kinase (JNK) and p38 kinase were increased compared with intrinsically aged skin in the same individuals. Phospho-c-Jun levels and activator protein 1 activities in photoaged skin were also higher than in intrinsically aged skin. Moreover, catalase activity was found to be much reduced in primary dermal fibroblasts from photoaged skin, and as a result, H2O2 accumulated more in primary dermal fibroblasts in photoaged skin. In addition, treating primary dermal fibroblasts from photoaged skin with catalase reduced H2O2 levels, reversed aging-dependent MAP kinase changes, and inhibited matrix metalloproteinase (MMP)-1 expression. Our results indicate that the accumulation of reactive oxygen species due to catalase attenuation may be a critical aspect of the MAP kinase signaling changes that may lead to skin aging and photoaging in human skin in vivo. Thus, the induction and regulation of endogenous antioxidant enzymes including catalase may offer a strategy for preventing and treating skin aging.

Adult↗

PubMed2004

Effect of minoxidil on proliferation and apoptosis in dermal papilla cells of human hair follicle.

BACKGROUND: Minoxidil has been widely used to treat androgenetic alopecia, but little is known about its pharmacological activity or about the identity of its target cells in hair follicles. We hypothesized that minoxidil has direct effects on the proliferation and apoptosis of dermal papilla cells (DPCs) of human hair follicle. OBJECTIVE: To elucidate the mechanism of topical minoxidil action in terms of stimulating hair growth. METHODS: We evaluated cell proliferations in cultured DPCs by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and measured the expressions of extracellular signal-regulated kinase (ERK), Akt, Bcl-2, and Bax by Western blot. We also measured elongation of hair follicles in organ culture. RESULTS: Minoxidil significantly increased the proliferation of DPCs. The levels of ERK phosphorylation and of phosphorylated Akt increased significantly 1 h post-treatment; percentage increase of ERK phosphorylation was 287% at 0.1 microM and 351% at 1.0 microM of minoxidil, and that of Akt phosphorylation was 168% at 0.1 microM and 257% at 1.0 microM of minoxidil. 1.0 microM of minoxidil increased Bcl-2 expression over 150%, while 1.0 microM of minoxidil decreased Bax expression by more than 50%. Moreover, a significant elongation of individual hair follicles in organ culture was observed after adding minoxidil. CONCLUSION: Minoxidil promotes the survival of human DPCs by activating both ERK and Akt and by preventing cell death by increasing the ratio of Bcl-2/Bax. We suggest that minoxidil stimulates the growth of human hairs by prolonging anagen through these proliferative and anti-apoptotic effects on DPCs.

Adult↗