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Background@#Fibroblasts produce collagen molecules that support the structure of the skin.The decrease and hypersynthesis of collagen causes skin problems such as skin atrophy, wrinkles and scars. @*Objective@#The purpose of this study is to investigate the mechanism of mitoxantrone on collagen synthesis in fibroblasts. @*Methods@#Cultured fibroblasts were treated with mitoxantrone, and then collagen synthesis was confirmed by reverse transcription-polymerase chain reaction and Western blot. @*Results@#Mitoxantrone inhibited the expression of type I collagen in fibroblasts at both the mRNA and protein levels. In the collagen gel contraction assay, mitoxantrone significantly inhibited gel contraction compared to the control group. Mitoxantrone inhibited transforming growth factor (TGF)-β-induced phosphorylation of SMAD3. Finally, mitoxantrone inhibited the expression of LARP6, an RNA-binding protein that regulates collagen mRNA stability. @*Conclusion@#These results suggest that mitoxantrone reduces collagen synthesis by inhibiting TGF-β/SMAD signaling and LARP6 expression in fibroblasts, which can be developed as a therapeutic agent for diseases caused by collagen hypersynthesis.
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Background@#Psoriasis is a chronic inflammatory skin disease. The etiology of psoriasis is not fully understood, but the genetic background is considered to be the most important factor. To date, many psoriasis-related genes have been discovered, but the role of many important genes has not been well understood. @*Objective@#The purpose of this study is to uncover possible roles of MDA5 in psoriasis. @*Methods@#Expression of MDA5 was investigated using immunohistochemistry. Then, MDA5 was overexpressed in keratinocytes using a recombinant adenovirus. @*Results@#As a result of immunohistochemical staining, the expression of MDA5 was significantly increased in the epidermis of psoriasis compared to normal skin. Similarly, the expression of MDA5 was increased in imiquimod-induced psoriasiform dermatitis model. In cultured keratinocytes, toll-like receptor 3 agonist poly(I:C) induced expression of MDA5 at both mRNA and protein levels. When MDA5 was overexpressed using a recombinant adenovirus, poly(I:C)-induced cytokine expression was significantly increased. Finally, MDA5 overexpression significantly inhibited calcium-induced differentiation of keratinocytes. @*Conclusion@#These results suggest that MDA5 increases in psoriasis and negatively regulates keratinocyte differentiation.
ABSTRACT
Background@#Psoriasis is a chronic inflammatory skin disease. The etiology of psoriasis is not fully understood, but the genetic background is considered to be the most important factor. To date, many psoriasis-related genes have been discovered, but the role of many important genes has not been well understood. @*Objective@#The purpose of this study is to uncover possible roles of MDA5 in psoriasis. @*Methods@#Expression of MDA5 was investigated using immunohistochemistry. Then, MDA5 was overexpressed in keratinocytes using a recombinant adenovirus. @*Results@#As a result of immunohistochemical staining, the expression of MDA5 was significantly increased in the epidermis of psoriasis compared to normal skin. Similarly, the expression of MDA5 was increased in imiquimod-induced psoriasiform dermatitis model. In cultured keratinocytes, toll-like receptor 3 agonist poly(I:C) induced expression of MDA5 at both mRNA and protein levels. When MDA5 was overexpressed using a recombinant adenovirus, poly(I:C)-induced cytokine expression was significantly increased. Finally, MDA5 overexpression significantly inhibited calcium-induced differentiation of keratinocytes. @*Conclusion@#These results suggest that MDA5 increases in psoriasis and negatively regulates keratinocyte differentiation.
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Background@#Sebocytes are the main cells involved in the pathogenesis of acne by producing lipids and inflammatory cytokines. Although palmitic acid (PA) has been suggested to induce an inflammatory reaction, its effect on sebocytes remains to be elucidated. @*Objective@#In the present study, we investigated whether PA promotes inflammasome-mediated inflammation of sebocytes both in vivo and in vitro. @*Methods@#We intradermally injected PA into the mice ears. And, we treated cultured human sebocytes with PA. Inflammasome-mediated inflammation was verified by immunohistochemistry, Western blot and ELISA. @*Results@#PA-treated mice developed an inflammatory response associated with increased interleukin (IL)-1β expression in the sebaceous glands. When PA was added to cultured human sebocytes, caspase-1 activation and IL-1β secretion were significantly enhanced. In addition, NLRP3 knockdown attenuated IL-1β production by sebocytes stimulated with PA. PA-mediated inflammasome activation required reactive oxygen species. @*Conclusion@#These findings indicate that PA activates the NLRP3 inflammasome before induction of an inflammatory response in sebocytes. Thus, PA may play a role in the inflammation of acne
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Background@#Psoriasis is a common chronic inflammatory skin disease. The development of psoriasis is dependent on many intercellular events such as innate immunity and T cell-mediated inflammation. Furthermore, genetic factors are strongly implicated in the pathophysiology of psoriasis. Although a variety of susceptible genes are identified, it is likely that many important genes remain undisclosed. @*Objective@#The aim of this study is to investigate the possible role of lysine demethylase 2A (KDM2A) in the pathophysiology of psoriasis. @*Methods@#We examined the expression of KDM2A using a well established imiquimod-induced psoriasiform dermatitis model. @*Results@#Immunohistochemistry analysis showed that expression of KDM2A was increased in imiquimod-induced psoriasiform dermatitis. Consistent with this result, KDM2A level was markedly increased in the epidermis of psoriatic patient. When keratinocytes were stimulated with TLR3 agonist poly(I:C), KDM2A was increased at both the mRNA and protein levels. Poly(I:C) increased the expression of psoriasis-related cytokines including tumor necrosis factor-α, interleukin-8, and CCL20, and KDM2A inhibitor daminozide enhanced the poly(I:C)-induced cytokine expression. Finally, topical co-application of imiquimod and daminozide exacerbated the imiquimod-induced psoriasiform dermatitis. @*Conclusion@#Together, these results suggest that KDM2A is increased to negatively regulate the inflammatory reaction of epidermal keratinocytes in psoriasis.
ABSTRACT
Exenatide extended-release was recently developed as an antidiabetic drug; it acts as a glucagon-like peptide-1 receptor agonist. A 54-year-old male visited our clinic complaining of a subcutaneous tender nodule on his left thigh that had developed over the course of 1 week. The patient had received exenatide extended-release injections for 5 months to treat diabetes. A histopathologic examination showed septal and lobular panniculitis with lymphohistiocyte and eosinophil infiltration. The patient was diagnosed with eosinophilic panniculitis (EP) due to exenatide extended- release injection. EP is a rare type of panniculitis characterized by a prominent infiltrate of eosinophils in the subcutaneous fat layer. It is a histologic reaction pattern that is associated with various clinical conditions. Among the injection- site reactions reported in exenatide extended-release users, injection-site nodules occur infrequently. Clinicians who treat diabetics who use exenatide extended-release should be aware of the possible occurrence of injection-site nodules.
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BACKGROUND: Alopecia areata (AA), a chronic, relapsing hair-loss disorder, is considered to be a T-cell-mediated autoimmune disease. Cold-inducible RNA-binding protein (CIRP) belongs to a family of cold-shock proteins that respond to cold stress, and has been identified as a damage-associated molecular pattern (DAMP) molecule that triggers the inflammatory response. Recent studies have shown that high-mobility group box 1, another DAMP molecule, is elevated in serum and scalp tissue of AA patients, suggesting a relationship between DAMP molecules and the pathogenesis of AA. OBJECTIVE: To investigate the clinical significance of serum CIRP levels in AA. METHODS: The serum levels of CIRP were compared between 68 patients with AA and 20 healthy controls. Additionally, the correlation between CIRP level and various clinical parameters was evaluated. RESULTS: The serum CIRP levels were significantly higher in AA patients compared to healthy subjects. Moreover, there was an association between the serum CIRP level and clinical characteristics, such as disease duration and disease activity. However, there was no significant difference in the serum CIRP level among the clinical types of AA (AA multiplex, alopecia totalis, and alopecia universalis). CONCLUSION: These results suggest that CIRP may play a significant role in the pathogenesis of AA and could be a potential biologic marker for monitoring the disease activity of AA.
Subject(s)
Humans , Alopecia Areata , Alopecia , Autoimmune Diseases , Biomarkers , Healthy Volunteers , Inflammation , RNA-Binding Proteins , ScalpABSTRACT
No abstract available.
Subject(s)
Carcinoma, Squamous Cell , Cyclic AMP Response Element-Binding Protein , Epithelial CellsABSTRACT
The authors would like to change the corresponding author of the article.
ABSTRACT
BACKGROUND: Psoriasis is a chronic inflammatory skin disease with an incidence of 0.5~3% of the worldwide population. The pathogenesis of psoriasis is related to dysregulated keratinocyte function and immune reactions. Notably, genetic factors are considered important etiological contributors. Globally, several researchers have recently performed genome-wide association studies (GWAS) to identify the genes related with psoriasis. OBJECTIVE: We aimed to investigate the expression pattern of 2 candidate genes that were identified by GWAS. These include interleukin 28 receptor alpha (IL28RA) and CUB and Sushi multiple domains 1 (CSMD1). METHODS: We applied imiquimod cream to develop a psoriasis-like mouse model and obtained skin tissue. We performed immunohistochemistry to detect the expression of IL-28A and CSMD1. RESULTS: IL28RA expression increased at an early time point such as 1 day after the topical application of 5% imiquimod cream. However, its expression returned to baseline levels 2 weeks after the topical application of imiquimod cream. CSMD1 expression also increased after the topical application of imiquimod, with increased expression particularly observed in the upper epidermal layer. Notably, CSMD1 expression decreased 7 days after imiquimod cream application. CONCLUSION: These results suggest that IL28RA and CSMD1 may play key roles in the pathogenesis of psoriasis.
Subject(s)
Animals , Mice , Gene Expression , Genome-Wide Association Study , Immunohistochemistry , Incidence , Interleukins , Keratinocytes , Psoriasis , Skin , Skin DiseasesABSTRACT
BACKGROUND: Skin hydration is a common problem both in elderly and young people as dry skin may cause irritation, dermatological disorders, and wrinkles. While both genetic and environmental factors seem to influence skin hydration, thorough genetic studies on skin hydration have not yet been conducted. OBJECTIVE: We used a genome-wide association study (GWAS) to explore the genetic elements underlying skin hydration by regulating epidermal differentiation and skin barrier function. METHODS: A GWAS was conducted to investigate the genetic factors influencing skin hydration in 100 Korean females along with molecular studies of genes in human epidermal keratinocytes for functional study in vitro. RESULTS: Among several single nucleotide polymorphisms identified in GWAS, we focused on Single Stranded DNA Binding Protein 3 (SSBP3) which is associated with DNA replication and DNA damage repair. To better understand the role of SSBP3 in skin cells, we introduced a calcium-induced differentiation keratinocyte culture system model and found that SSBP3 was upregulated in keratinocytes in a differentiation dependent manner. When SSBP3 was overexpressed using a recombinant adenovirus, the expression of differentiation-related genes such as loricrin and involucrin was markedly increased. CONCLUSION: Taken together, our results suggest that genetic variants in the intronic region of SSBP3 could be determinants in skin hydration of Korean females. SSBP3 represents a new candidate gene to evaluate the molecular basis of the hydration ability in individuals.
Subject(s)
Aged , Female , Humans , Adenoviridae , Cell Differentiation , DNA Damage , DNA Replication , DNA, Single-Stranded , DNA-Binding Proteins , Genome-Wide Association Study , In Vitro Techniques , Introns , Keratinocytes , Polymorphism, Single Nucleotide , SkinABSTRACT
Hair graying is an obvious sign of human aging. Although graying has been investigated extensively, the mechanism remains unclear. Here, we reviewed previous studies on the mechanism of graying and seek to offer some new insights. The traditional view is that hair graying is caused by exhaustion of the pigmentary potential of the melanocytes of hair bulbs. Melanocyte dysfunction may be attributable to the effects of toxic reactive oxygen species on melanocyte nuclei and mitochondria. A recent study suggests that bulge melanocyte stem cells (MSCs) are the key cells in play. Graying may be caused by defective MSC self-maintenance, not by any deficiency in bulbar melanocytes. Our previous study suggested that graying may be principally attributable to active hair growth. Active hair growth may produce oxidative or genotoxic stress in hair bulge. These internal stress may cause eventually depletion of MSC in the hair follicles. Taken together, hair graying may be caused by MSC depletion by genotoxic stress in the hair bulge. Hair graying may also be sometimes caused by dysfunction of the melanocytes by oxidative stress in the hair bulb. In addition, hair graying may be attributable to MSC depletion by active hair growth.
Subject(s)
Humans , Aging , DNA Damage , Hair Follicle , Hair , Melanocytes , Mitochondria , Oxidative Stress , Reactive Oxygen Species , Rivers , Stem CellsABSTRACT
Cutis marmorata telangiectatica congenita (CMTC) is a rare congenital vascular disorder. The skin lesions associated with CMTC include persistent, reticulated vascular patches and telangiectasia, and they are sometimes associated with underlying atrophy and ulceration. The condition is present at birth and tends to improve with age, although some skin lesions remain unchanged throughout life. We encountered two patients with CMTC: a 12-day-old infant and a 21-year-old woman with a history of CMTC since birth. Both patients had localized reticulated purpuric patches with atrophy. During follow-up, although the purpuric patches improved in both patients, there were no changes in the skin atrophy in either patient. Herein, we present these cases showing the changes in the cutaneous features of CMTC over time and demonstrate that CMTC at birth may persist throughout life.
Subject(s)
Female , Humans , Infant , Young Adult , Atrophy , Follow-Up Studies , Parturition , Skin , Telangiectasis , UlcerABSTRACT
BACKGROUND: Micro-needle patches have been recently used to increase skin permeability, which improves drug delivery, and for cosmetic purposes. However, these patches may often have limited efficacy due to insufficient skin penetration and reduced compliance caused by discomfort. OBJECTIVE: We evaluated the efficacy and the safety of soluble micro-spicule containing epidermal growth factor (MS-EGF) for the treatment of periocular wrinkles. METHODS: Twenty healthy volunteers aged 33 to 54 years were enrolled in a randomized, controlled, split-face study. For 4 weeks, a periocular wrinkle was treated daily with either a soluble MS-EGF cream or a cream containing EGF alone. All subjects underwent 8 weeks of follow-up. Efficacy was assessed using an ultrasonic measurement of dermal depth and density, digital skin image analysis, 5-point photonumeric scale for periocular wrinkles and subjective satisfaction. RESULTS: MS-EGF group showed statistically significant increase of dermal depth and density compared to EGF alone group after 4 and 8 weeks. In addition, there was a marked improvement shown in clinical and 3-dimensional skin image in MS-EGF group. The treatments were well-tolerated; no significant side-effect was noted. CONCLUSION: The MS-EGF formulation may represent an effective and biocompatible advance in the treatment of periocular wrinkles.