-
Journal of the American Academy of Dermatology 04/2013; 68(4):e139-40. · 3.99 Impact Factor
-
Journal of the American Academy of Dermatology 04/2013; 68(4):e137-8. · 3.99 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The skin has many important functions such as protection, preservation, temperature regulation, and vitamin D synthesis. It is composed of a variety of cell types including keratinocytes, melanocytes and fibroblasts.
We attempted to compare the gene expression profiles between keratinocytes, melanocytes and fibroblast, using cDNA microarray.
Keratinocytes, melanocytes and fibroblasts were primary cultured from five foreskin specimens. Total RNAs were extracted and pooled to reduce the individual variations, and then used for cDNA microarray.
Total 12,028 genes were selected as the reliable genes whose expression was detected in at least one of the three cell types. By comparing the relative expression levels with cutoff limitation as a fourfold change, we obtained 126 fibroblast-specific, 179 keratinocyte-specific and 173 melanocyte-specific genes, many of which are known to be characteristically expressed in each cell type. In addition, we identified many genes whose skin-specific functions have not yet been determined.
Our data provide important information on which to base further investigation into the specification of skin cell types.
Annals of Dermatology 02/2013; 25(1):36-45. · 0.53 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A 28-year-old Asian male was referred for dermatologic evaluation of diffuse bluish-red maculopapules in the lower trunk and genital regions. There was no family history, and with the exception of dispersed skin lesions and hypohidrosis, no other complaints or symptoms were present. Histological evaluation of the skin lesions revealed angiokeratomas. When this combination of clinical and histological findings is observed, Fabry disease is suspected. Biochemical examination performed for definitive diagnosis did not show any activity of the α-galactosidase A enzyme. Through identification of a c.182_183ins(GA) mutation of the GLA gene, Fabry disease was diagnosed. However, there was no particular abnormal finding with regard to the evaluation of non-cutaneous manifestations, a symptom that can occur in the progress of this disease. We reported a case of Fabry disease, restricted to the dermatologic presentation, involving a novel frameshift mutation in the GLA gene.
Annals of Dermatology 02/2013; 25(1):95-8. · 0.53 Impact Factor
-
Ge Shi,
Kyung-Cheol Sohn,
Zhengjun Li,
Dae-Kyoung Choi,
Young Min Park,
Jin-Hwa Kim,
Yi-Ming Fan,
Yong Hee Nam,
Sooyeon Kim,
Myung Im,
Young Lee,
Young-Joon Seo,
Chang Deok Kim, Jeung-Hoon Lee
[show abstract]
[hide abstract]
ABSTRACT: In this study, we investigated the expression and putative role of Sox9 in epidermal keratinocyte. Immunohistochemical staining showed that Sox9 is predominantly expressed in the basal layer of normal human skin epidermis, and highly expressed in several skin diseases including psoriasis, basal cell carcinoma, keratoacanthoma and squamous cell carcinoma. In calcium-induced keratinocyte differentiation model, the expression of Sox9 was decreased in a time dependent manner. When Sox9 was overexpressed using a recombinant adenovirus, cell growth was enhanced, while the expression of differentiation-related genes such as loricrin and involucrin was markedly decreased. Similarly, when rat skin was intradermally injected with the adenovirus expressing Sox9, the epidermis was thickened with increase of PCNA positive cells, while the epidermal differentiation was decreased. Finally, UVB irradiation induced Sox9 expression in cultured human epidermal keratinocytes, and keratinocytes are protected from UVB-induced apoptosis by Sox9 overexpression. Together, these results suggest that Sox9 is an important regulator of epidermal keratinocytes with putative pro-proliferation and/or pro-survival functions, and may be related to several cutaneous diseases that are characterized by abnormal differentiation and hyperproliferation.
PLoS ONE 01/2013; 8(1):e54355. · 4.09 Impact Factor
-
Journal of the American Academy of Dermatology 01/2013; 68(1):e3-4. · 3.99 Impact Factor
-
Annals of Dermatology 11/2012; 24(4):476-8. · 0.53 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Epigenetic modulation of gene expression occurs by various methods, including DNA methylation and histone modification. DNA methylation of specific genes may affect the chromatin structure, preventing access by the transcriptional machinery. Although gene expression is dramatically changed during keratinocyte differentiation, there is no evidence of epigenetic modulation during the process of epidermal stratification.
We investigated whether epigenetic modulation is involved in keratinocyte differentiation-specific gene regulation.
We used trypsin to produce epidermal fragmentation (named T1-T4) and performed a morphological analysis using hematoxylin-eosin stain and cytokeratin expression based on reverse transcription polymerase chain reaction. We then constructed a DNA methylation microarray.
Each epidermal fragment showed morphological features of the epithelial layer. T1 represented the basal layer, T2 was the spinous layer, T3 was the granular layer, and T4 was the cornified layer. The level of the K14 proliferation marker was increased in the T1 fraction, and the level of K10 differentiation marker was increased in the T2-T4 fractions. Using a methylation microarray with the T1 and T4 fractions, we obtained many hypermethylated and hypomethylated genes from differentiated keratinocytes.
The importance of epigenetic modulation in target gene expression during keratinocyte differentiation is identified.
Annals of Dermatology 08/2012; 24(3):261-6. · 0.53 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The use of botulinum toxin type A (BoNT) continues to expand. Some physicians have noted a face-lifting effect after intradermal injection of BoNT, although the effects are controversial.
To investigate the in vitro effects of BoNT on human dermal fibroblasts.
The proliferation and toxic effects of BoNT on human dermal fibroblasts were measured. To understand the mechanism of BoNT on collagen production of fibroblasts, procollagen type I carboxy-terminal peptide (PIP) was measured using enzyme-linked immunosorbent assay, and collagen production was monitored using Western blotting. To examine the effect of BoNT on collagen degradation, we evaluated matrix metalloproteinase (MMP) production using gelatin zymography.
BoNT did not stimulate the proliferation of or show toxic effects on human dermal fibroblasts. Levels of PIP increased significantly in fibroblasts grown in the presence of BoNT, and BoNT upregulated the expression of type I collagen and decreased the production of some MMPs in fibroblasts that prevent collagen degradation.
This study shows interesting effects of BoNT on collagen production and degradation of human dermal fibroblasts in vitro. This research provides the experimental background for using intradermal BoNT injection for remodeling of dermal tissues in aged skin.
Dermatologic Surgery 06/2012; 38(10):1689-94. · 1.80 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The biochemical mechanism by which the human tumorous imaginal disc1(S) (hTid-1(S)) interferes with actin cytoskeleton organization in keratinocytes of human skin epidermis was investigated. We found that hTid-1, specifically hTid-1(S), interacts with MK5, a p38-regulated/activated protein kinase, and inhibits the protein kinase activity of MK5 that phosphorylates heat shock protein HSP27 in cultured HeLa cells. Thus, hTid-1(S) expression inhibits the phosphorylation of HSP27 known to play important roles in F-actin polymerization and actin cytoskeleton organization. The interplay between MK5/HSP27 signaling and hTid-1(S) expression was supported by the inhibition of HSP27 phosphorylation and MK5 activity in HeLa cells in response to hypoxia during which hTid-1(S) expression was down-regulated. We also found that overexpression of hTid-1(S) results in the inhibition of HSP27 phosphorylation, F-actin polymerization, and actin cytoskeleton organization in transduced HaCaT keratinocytes. This study further proposes that the loss of hTid-1(S) expression in the basal layer of skin epidermis correlates with the enhanced HSP27 phosphorylation, keratinocyte hyperproliferation, and excess actin cytoskeleton organization in lesional psoriatic skin.
Journal of Biological Chemistry 06/2012; 287(31):25954-63. · 4.77 Impact Factor
-
Young Lee,
Sunhyae Jang,
Jeong-Ki Min,
Kyungmin Lee,
Kyung-Cheol Sohn,
Jong-Soon Lim,
Myung Im,
Hae-Eul Lee,
Young-Joon Seo,
Chang-Deok Kim, Jeung-Hoon Lee
[show abstract]
[hide abstract]
ABSTRACT: S100A8 and S100A9 are members of the S100A8 protein family that exist as homodimers and heterodimers in neutrophils, monocytes, and macrophages. Recent studies have shown the pivotal roles of S100A8 and S100A9 in the propagation of inflammation and keratinocyte proliferation in psoriasis. We found significant up-regulation of S100A8 and S100A9 secretion from keratinocytes in psoriatic lesions. To mimic the in vivo secretory conditions of S100A8 and S100A9 from psoriatic epidermal keratinocytes, we used the culture medium (CM) of S100A8 and S100A8/A9 adenovirus-transduced keratinocytes to investigate the functions of S100A8 and S100A9. We detected increased levels of various pro-inflammatory cytokines in the CM, including IL-8 and TNF-α, which are involved in aggravating psoriatic skin lesions, and IL-6 and members of the CXCL family of pro-angiogenic cytokines. The CM increased immune cell migration and increased angiogenesis in human umbilical vein endothelial cells. In conclusion, we found that the upregulated production of S100A8 and S100A9 by psoriatic epidermal keratinocytes activated adjacent keratinocytes to produce several cytokines. Moreover, S100A8 and S100A9 themselves function as pro-angiogenic and chemotactic factors, generating a psoriatic milieu in skin.
Biochemical and Biophysical Research Communications 06/2012; 423(4):647-53. · 2.48 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Aquaporins (AQPs) are a family of water transporting proteins present in many mammalian epithelial and endothelial cell types. Among the AQPs, AQP3 is known to be a water/glycerol transporter expressed in human skin.
The relationship between the expression level of AQP3 and transpidermal water loss (TEWL) in the lesional and peri-lesional skin of psoriasis-affected patients, and skin hydration in the lesional and peri-lesional skin of psoriasis patients, was investigated.
The expression of AQP3 in psoriasis-affected and healthy control skin was determined using immunohistochemical and immunofluroscence staining. TEWL and skin hydration were measured using a Tewameter® TM210 (Courage & Khazaka, Cologne, Germany) and a Corneometer® CM 820 (Courage & Khazaka), respectively.
AQP3 was mainly expressed in the plasma membrane of stratum corneum and the stratum spinosum in normal epidermis. Unlike the normal epidermis, AQP3 showed decreased expression in the lesional and peri-lesional epidermis of psoriasis. TEWL was increased, and skin hydration was decreased, in the lesional and peri-lesional skin of psoriasis patients, compared with the healthy control sample.
Although various factors contribute to reduced skin hydration in the lesional and peri-lesional skin of psoriasis, AQP3 appears to be a key factor in the skin dehydration of psoriasis-affected skin.
Annals of Dermatology 05/2012; 24(2):168-74. · 0.53 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Aberrant DNA methylation occurs early and frequently in tumorigenesis. Identification of DNA methylation biomarkers is a field that provides potential for improving the clinical process of breast cancer diagnosis. We utilized a genome-wide technique, methylated DNA isolation assay (MeDIA), in combination with high-resolution CpG microarray analysis to identify hypermethylated genes in breast cancer. Among differentially methylated genes between tumor and adjacent normal tissues, 3 candidate genes (LHX2, WT1 and OTP) were finally selected through a step-wise filtering process and examined for methylation status in normal tissues, primary tumor, and paired adjacent normal-appearing tissues from 39 breast cancer patients. Based on the calculated cut-off values, all genes showed significantly higher frequencies of aberrant hypermethylation in primary tumors (43.6% for LHX2, 89.7% for WT1 and 100% for OTP, p<0.05) while frequencies were intermediate in paired adjacent normal tissues and absent in normal tissues. On further analysis, the methylation level in primary tumors was not significantly correlated with clinicopathological features. Interestingly, DNA methylation of a novel gene OTP was detected in adjacent normal tissues even 6 cm away from primary tumors, suggesting that OTP methylation may qualify as a biomarker for the early detection of breast cancer. In conclusion, we successfully identified a novel gene OTP frequently methylated in breast cancer by genome-wide screening. Our results suggest that the OTP gene may play a crucial role in breast carcinogenesis, although further clinical validation will be needed to evaluate the potential application of OTP in the early detection of breast cancer.
Oncology Reports 05/2012; 27(5):1681-8. · 1.84 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Recently, autologous platelet-rich plasma (PRP) has attracted attention in various medical fields, including plastic and orthopedic surgery and dermatology, for its ability to promote wound healing. PRP has been tested during facelift and hair transplantation to reduce swelling and pain and to increase hair density.
To investigate the effects of PRP on hair growth using in vivo and in vitro models.
PRP was prepared using the double-spin method and applied to dermal papilla (DP) cells. The proliferative effect of activated PRP on DP cells was measured. To understand the mechanisms of activated PRP on hair growth, we evaluated signaling pathways. In an in vivo study, mice received subcutaneous injections of activated PRP, and their results were compared with control mice.
Activated PRP increased the proliferation of DP cells and stimulated extracellular signal-regulated kinase (ERK) and Akt signaling. Fibroblast growth factor 7 (FGF-7) and beta-catenin, which are potent stimuli for hair growth, were upregulated in DP cells. The injection of mice with activated PRP induced faster telogen-to-anagen transition than was seen on control mice.
Although few studies tested the effects of activated PRP on hair growth, this research provides support for possible clinical application of autologous PRP and its secretory factors for promotion of hair growth.
Dermatologic Surgery 03/2012; 38(7 Pt 1):1040-6. · 1.80 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The extracellular matrix (ECM) produced by dermal fibroblasts supports skin structure, and degradation and/or reduced production of ECM are the main causes of wrinkle formation.
The aim of this study was to identify the active ingredient that enhances ECM production in dermal fibroblasts.
Polarity-based fractionation was used to isolate the active ingredient from natural extracts, and the effects of cedrol (isolated from Pterocarpus indicusirginia) on ECM production in cultured human dermal fibroblasts was investigated by reverse transcription-polymerase chain reaction, enzyme linked immunosorbent assay, and Western blot analysis.
Cedrol accelerated fibroblast growth in a dose-dependent manner and increased the production of type 1 collagen and elastin. Phosphorylation of p42/44 extracellular signal-regulated kinase, p38 mitogen-activated protein kinase, and Akt was markedly increased by cedrol, indicating that enhanced ECM production is linked to activation of intracellular signaling cascades.
These results indicate that cedrol stimulates ECM production, with possible applications to the maintenance of skin texture.
Annals of Dermatology 02/2012; 24(1):16-21. · 0.53 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Hair regression and balding are distressing concerns for an increasing number of people due to changes in lifestyle and serious nutritional imbalances. Therapies for treatment of hair loss are needed. Among potential therapeutics, adenosine has been suggested as a potent regulator of hair growth. In this study, we investigated the effects of adenosine on hair follicles and dermal papilla (DP) cells, and the mechanism underlying the action of adenosine. Hair follicles are organs, including DP cells, that are responsible for the production of hair fibers by inducing and maintaining the hair growth phase (anagen). In a culture of DP cells in vitro, adenosine stimulated proliferation of DP cells by increasing thymidine uptake. Subsequently, adenosine activated and elongated the anagen phase by increasing the uptake of radiolabeled cysteine in an organ culture of mouse vibrissae hair follicles. We also confirmed that adenosine promoted the expression of several growth factors that are responsible for hair growth, including fibroblast growth factors (FGF)-7, FGF-2, insulin-like growth factor (IGF)-1, and vascular endothelial growth factor (VEGF) in a cDNA microarray with semi-quantitative RT-PCR. Transcriptional activation of β-catenin in DP cells was increased by adenosine in a luciferase assay. β-catenin is a co-activator of Wnt/β-catenin signaling that induces morphogenesis and differentiation of hair follicles and also acts to transactivate downstream signaling pathways, including the ERK pathway. Using Western blotting, we found that adenosine stimulated phosphorylation of ERK, CREB and AKT. These results suggest that adenosine stimulates growth of hair follicles by triggering the expression of growth factors and β-catenin, and by inducing their downstream target signaling pathways.
International Journal of Molecular Medicine 02/2012; 29(2):195-201. · 1.98 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Imatinib mesylate (Gleevec™, STI571), a selective inhibitor of BCR-ABL, c-Kit, and platelet-derived factor receptor, has been used to treat chronic myelogenous leukemia (CML) and gastrointestinal stromal tumors. Although its use has been associated with various adverse cutaneous reactions, pityriasis rosea-like drug eruptions are rare. Here, we report a case of pityriasis rosea-like drug eruption that developed following the administration of imatinib mesylate to treat CML.
Annals of Dermatology 12/2011; 23(Suppl 3):S360-3. · 0.53 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The principles determining the primary localization of lesions in fixed drug eruption (FDE) are still unknown. Studies investigating the predilection areas in FDE have indicated drug-related, trauma-related, or inflammation-related specific site involvement, as well as visceracutaneous reflex-related specific site involvement. The importance of viscerocutaneous reflexes for the location of dermatoses was first recognized in the 1960s. Head's zones are viscerocutaneous reflex projection fields on the skin that extend over certain dermatomes and possess a reflex-associated maximal point. Recently, in a Turkish collective of patients, three women with the primary location of FDE lesions on the maximal points of Head's zones were presented. We also experienced 3 cases with FDE where the lesions were located at specific sites (buttocks), the so-called maximal points of Head's zones, which are known to be the most active dermatomal areas of an underlying visceral pathology. An underlying internal disturbance (ureter stone, pyelonephritis and chronic pelvic inflammatory disease) was found in all 3 patients, corresponding to the organ-related maximal point of Head's zones in each case. In conclusion, the primary location of FDE lesions on the maximal points of Head's zones revealed relevant organ disorders with corresponding projection fields.
Annals of Dermatology 12/2011; 23(Suppl 3):S383-6. · 0.53 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Classic Kaposi sarcoma (KS) is a rare human herpes virus 8-associated angioproliferative disease, and the disseminated classic type of KS in Korea is even rarer. The treatment options for classic KS vary and range from surgical excision to ionizing irradiation or chemotherapy. Recently, there have been a few reports of treating classic KS with paclitaxel, which has been used to treat AIDS-associated KS and post-transplant KS. We herein report a case of disseminated classic type KS in a 78-year-old Korean male patient who showed dramatic response after only two cycles of paclitaxel treatment.
Annals of Dermatology 11/2011; 23(4):504-7. · 0.53 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Autologous platelet-rich plasma has attracted attention in various medical fields recently, including orthopedic, plastic, and dental surgeries and dermatology for its wound healing ability. Further, it has been used clinically in mesotherapy for skin rejuvenation.
In this study, the effects of activated platelet-rich plasma (aPRP) and activated platelet-poor plasma (aPPP) have been investigated on the remodelling of the extracellular matrix, a process that requires activation of dermal fibroblasts, which is essential for rejuvenation of aged skin.
Platelet-rich plasma (PRP) and platelet-poor plasma (PPP) were prepared using a double-spin method and then activated with thrombin and calcium chloride. The proliferative effects of aPRP and aPPP were measured by [(3)H]thymidine incorporation assay, and their effects on matrix protein synthesis were assessed by quantifying levels of procollagen type I carboxy-terminal peptide (PIP) by enzyme-linked immunosorbent assay (ELISA). The production of collagen and matrix metalloproteinases (MMP) was studied by Western blotting and reverse transcriptase-polymerase chain reaction.
Platelet numbers in PRP increased to 9.4-fold over baseline values. aPRP and aPPP both stimulated cell proliferation, with peak proliferation occurring in cells grown in 5% aPRP. Levels of PIP were highest in cells grown in the presence of 5% aPRP. Additionally, aPRP and aPPP increased the expression of type I collagen, MMP-1 protein, and mRNA in human dermal fibroblasts.
aPRP and aPPP promote tissue remodelling in aged skin and may be used as adjuvant treatment to lasers for skin rejuvenation in cosmetic dermatology.
Annals of Dermatology 11/2011; 23(4):424-31. · 0.53 Impact Factor