RESUMO
Pulmonary arterial hypertension (PAH) is a life-threatening condition characterized by a progressive increase in pulmonary vascular resistance leading to right ventricular failure and often death. Here we report that deficiency of transcription factor GATA6 is a shared pathological feature of PA endothelial (PAEC) and smooth muscle cells (PASMC) in human PAH and experimental PH, which is responsible for maintenance of hyper-proliferative cellular phenotypes, pulmonary vascular remodeling and pulmonary hypertension. We further show that GATA6 acts as a transcription factor and direct positive regulator of anti-oxidant enzymes, and its deficiency in PAH/PH pulmonary vascular cells induces oxidative stress and mitochondrial dysfunction. We demonstrate that GATA6 is regulated by the BMP10/BMP receptors axis and its loss in PAECs and PASMC in PAH supports BMPR deficiency. In addition, we have established that GATA6-deficient PAEC, acting in a paracrine manner, increase proliferation and induce other pathological changes in PASMC, supporting the importance of GATA6 in pulmonary vascular cell communication. Treatment with dimethyl fumarate resolved oxidative stress and BMPR deficiency, reversed hemodynamic changes caused by endothelial Gata6 loss in mice, and inhibited proliferation and induced apoptosis in human PAH PASMC, strongly suggesting that targeting GATA6 deficiency may provide a therapeutic advance for patients with PAH.
Assuntos
Proteínas Morfogenéticas Ósseas , Fator de Transcrição GATA6 , Estresse Oxidativo , Hipertensão Arterial Pulmonar , Animais , Camundongos , Proteínas Morfogenéticas Ósseas/genética , Proteínas Morfogenéticas Ósseas/metabolismo , Proliferação de Células , Células Cultivadas , Hipertensão Pulmonar Primária Familiar/patologia , Fator de Transcrição GATA6/genética , Fator de Transcrição GATA6/metabolismo , Miócitos de Músculo Liso/metabolismo , Hipertensão Arterial Pulmonar/genética , Hipertensão Arterial Pulmonar/metabolismo , Hipertensão Arterial Pulmonar/patologia , Artéria Pulmonar/patologia , Remodelação VascularRESUMO
Systemic sclerosis (SSc) is a chronic autoimmune disease characterised by fibrosis, inflammation and vasculopathy in the skin and internal organs. Recently, several articles described that Th17 cells, IL-23 and IL-17 levels were significantly elevated in the peripheral blood or fibrotic sites of SSc. We report a case of SSc and psoriasis administered ustekinumab, IL-12/IL-23 inhibitor. In this case, the skin tightening was successfully improved and ustekinumab was more effective, even though oral prednisolone (9-12 mg/day) had some effect on skin tightening and arthralgia. We consider that inhibition of Th17 cytokines may lead to therapeutic efficacy against SSc. Ustekinumab has the potential for a treatment option of SSc.
Assuntos
Interleucina-12/antagonistas & inibidores , Interleucina-23/antagonistas & inibidores , Psoríase/tratamento farmacológico , Escleroderma Sistêmico/tratamento farmacológico , Pele/efeitos dos fármacos , Ustekinumab/uso terapêutico , Humanos , Interleucina-23/sangue , Masculino , Pessoa de Meia-Idade , Psoríase/imunologia , Escleroderma Sistêmico/imunologia , Pele/patologia , Células Th17/fisiologiaRESUMO
These days various collagen supplements have widely been marketed. However, it has not been scientifically proved whether increasing collagen can actually prevent skin aging. Systemic sclerosis (SSc) is an autoimmune disease that is characterized by thickening of the skin caused by accumulation of collagen. In this study, we tried to evaluate facial skin characteristics and skin aging of SSc patients by using digital imaging system. As the result, the severity of wrinkles, texture and pores were significantly lower in SSc patients than control subjects. Among them, wrinkles showed better correlation with skin thickness score. Therefore, increased amount of collagen in scleroderma skin may directly affect wrinkles. In conclusion, attempt on collagen induction itself is reasonable and effective strategy in order to keep young appearance, although oral collagen supplementation may not directly reach to the skin.
Assuntos
Face/patologia , Processamento de Imagem Assistida por Computador , Fotografação , Escleroderma Sistêmico/patologia , Envelhecimento da Pele/patologia , Pele/patologia , Idoso , Estudos de Casos e Controles , Colágeno , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/metabolismo , Pele/metabolismoRESUMO
Infliximab is an anti-tumor necrosis factor (TNF)-α antibody drug that suppresses TNF-α and its associated inflammatory responses. Although infliximab therapy generally results in a 75% or greater improvement in the Psoriasis Area and Severity Index from baseline in psoriasis patients, there is the heterogeneity of therapeutic efficacy in psoriasis patients among patients of a similar PASI baseline score. However, there are few published reports about the predictors of the clinical response among psoriasis patients who undergo biologic therapies. We thus evaluated the possible existence of biologic markers that would indicate poor prognosis of infliximab using skin biopsy specimens. This was because we assumed that the inhibitors for upregulated chemokine/chemokine receptors in non-responders may have the ability to reduce the occurrence of psoriatic eruptions. PCR array analyses identified that the levels of various chemokines and chemokine receptors were increased in non-responders in comparison to responders. Immunohistochemical analyses revealed that upregulation of the CCR9 protein levels was not associated with the pretherapeutic PASI score, but with poor response to infliximab. Our results indicated that the expression levels of CCR9 in lesional skin may be a useful biologic marker of the clinical efficacy of infliximab therapy in psoriasis patients.
Assuntos
Biomarcadores Farmacológicos/metabolismo , Fármacos Dermatológicos/uso terapêutico , Infliximab/uso terapêutico , Psoríase/tratamento farmacológico , Receptores CCR/metabolismo , Pele/metabolismo , Adulto , Biópsia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Psoríase/metabolismo , Psoríase/patologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Pele/patologia , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
BACKGROUND: The diagnosis of dermatomyositis is sometimes difficult. We tried to evaluate the possibility that levels of Homo sapiens microRNA-214 (hsa-miR-214) in hair roots or hair shafts can be a useful marker of the disease. METHODS: A single hair root and five pieces of hair shafts were obtained from nine patients with dermatomyositis, 15 normal subjects, and 18 patients with scleroderma before treatment. RNAs were purified from the hair roots and hair shafts using commercially available kits. cDNA was synthesized from the RNA, and miR-214 levels were measured with quantitative real-time polymerase chain reaction. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic performance of hair microRNA levels. RESULTS: The levels of miR-214 in hair shafts of patients with dermatomyositis were significantly higher than those of normal subjects and patients with scleroderma. By receiver operator curve analysis of hair shaft miR-214 levels to distinguish patients with dermatomyositis from normal subjects, the area under the curve was 0.90. The duration between symptom onset and the first visit to the hospital was significantly shorter in patients with elevated hair shafts miR-214 levels, suggesting that they have more severe subjective symptoms. On the other hand, we could not find significant differences in hair root miR-214 levels among normal subjects and patients with dermatomyositis and scleroderma. CONCLUSIONS: Hair shaft miR-214 levels are useful for diagnosis and evaluating the disease severity of dermatomyositis. Hair microRNA levels may have potential to be a novel and less invasive biomarker.
Assuntos
Dermatomiosite/diagnóstico , Dermatomiosite/metabolismo , Cabelo/química , MicroRNAs/análise , Escleroderma Sistêmico/metabolismo , Adulto , Idoso , Área Sob a Curva , Biomarcadores/análise , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Adulto JovemRESUMO
Recent studies have shown that immunotherapies and molecular targeted therapies are effective for advanced melanoma. Non-antigen-specific immunotherapies such as immunocheckpoint blockades have been shown to be effective in the treatment of advanced melanoma. However, the response rates remain low. To improve their efficacy, they should be combined with antigen-specific immunotherapy. Elevated expression of the transcription factor, Forkhead box M1 (FOXM1), has been reported in various human cancers, and it has been shown to have potential as a target for immunotherapy. The purpose of this study was to investigate the FOXM1 expression in human melanoma samples and cell lines, to evaluate the relationship between the FOXM1 expression and the clinical features of melanoma patients and to investigate the association between the FOXM1 and MAPK and PI3K/AKT pathways in melanoma cell lines. We conducted the quantitative reverse transcription PCR (qRT-PCR) and Western blotting analyses of melanoma cell lines, and investigated melanoma and nevus tissue samples by qRT-PCR and immunohistochemistry. We performed MEK siRNA and PI3K/AKT inhibitor studies and FOXM1 siRNA studies in melanoma cell lines. We found that FOXM1 was expressed in all of the melanoma cell lines, and was expressed in 49% of primary melanomas, 67% of metastatic melanomas and 10% of nevi by performing immunohistochemical staining. Metastatic melanoma samples exhibited significantly higher mRNA levels of FOXM1 (p = 0.004). Primary melanomas thicker than 2 mm were also more likely to express FOXM1. Patients whose primary melanoma expressed FOXM1 had a significantly poorer overall survival compared to patients without FOXM1 expression (p = 0.024). Downregulation of FOXM1 by siRNA significantly inhibited the proliferation of melanoma cells, and blockade of the MAPK and PI3K/AKT pathways decreased the FOXM1 expression in melanoma cell lines. In conclusion, FOXM1 is considered to be a new therapeutic target for melanoma.
Assuntos
Fatores de Transcrição Forkhead/biossíntese , Regulação Neoplásica da Expressão Gênica , Melanoma/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Criança , Pré-Escolar , Feminino , Proteína Forkhead Box M1 , Fatores de Transcrição Forkhead/genética , Humanos , Lactente , Sistema de Sinalização das MAP Quinases/genética , Masculino , Melanoma/genética , Melanoma/patologia , Melanoma/terapia , Pessoa de Meia-Idade , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Metástase Neoplásica , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
BACKGROUND: Toxic epidermal necrolysis (TEN) is a lethal complication of drugs, thus early diagnosis and treatment are important. However, there are no satisfactory clinical biomarkers of TEN. OBJECTIVES: We investigated miR-124 and miR-214 expressions in serum and skin tissues of severe drug eruptions to evaluate the possibility of biomarkers of TEN. MATERIALS & METHODS: microRNAs were extracted from serum and skin tissues. Serum samples were obtained from 7 TEN patients, 5 Stevens-Johnson syndrome (SJS) patients, 11 erythema multiforme (EM) minor patients and 21 healthy volunteers. Skin tissues were obtained from 4 TEN patients, 3 SJS patients, 8 EM minor patients, 3 psoriasis and 3 atopic dermatitis patients. Six control skin samples were obtained. MicroRNA concentrations were determined by PCR array and real-time PCR. RESULTS: The concentrations of miR-124 in sera from TEN were significantly higher than those from healthy controls. In the characteristics curve analysis of serum miR-124 for differentiating TEN patients from normal subjects, the area under curve was 0.94. The serum miR-124 concentration was strongly correlated with the erosion area and the SCORTEN scale. The expression of miR-214 was significantly increased in the skin of TEN. CONCLUSION: The serum miR-124 concentration can be used as a disease activity marker for severe drug eruptions, reflecting the severity of keratinocyte apoptosis.
Assuntos
Regulação da Expressão Gênica , MicroRNAs/genética , Síndrome de Stevens-Johnson/genética , Adulto , Área Sob a Curva , Estudos de Casos e Controles , Progressão da Doença , Feminino , Marcadores Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Curva ROC , Medição de Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Síndrome de Stevens-Johnson/sangue , Síndrome de Stevens-Johnson/fisiopatologia , Regulação para CimaRESUMO
Crizotinib is an oral small-molecule anaplastic lymphoma kinase (ALK) tyrosine-kinase inhibitor for the treatment of ALK-positive non-small-cell lung cancer (NSCLC). A 63-year old woman with postoperative relapsed ALK-positive NSCLC was treated with crizotinib. Erythema multiforme (EM) occurred one week after initiation of crizotinib therapy. Skin biopsy specimen showed compatible drug eruption. The discontinuation of crizotinib improved her eruption within one week. This report presented the first case of crizotinib-associated EM, which is the preclinical stage of Stevens-Johnson syndrome. Although crizotinib is clinically available, we should be aware of its potential severe skin adverse event.
Assuntos
Eritema Multiforme/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Pirazóis/efeitos adversos , Piridinas/efeitos adversos , Crizotinibe , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Localized scleroderma (LSc) exhibits fibrosis of the skin and subcutaneous tissue. LSc shows an excessive deposition of type 1 collagen. OBJECTIVES: To elucidate the mechanism of type 1 collagen overexpression in LSc, we investigated the epigenetics, focusing on microRNA (miRNA). MATERIALS & METHODS: miRNA expression profile was determined by PCR array analysis. The expression of microRNA-196a (miR-196a) in the skin tissue was examined by in situ hybridization or real-time PCR. The serum levels of miR-196a were measured by real-time PCR. RESULTS: PCR array analysis demonstrated that the miR-196a level was markedly decreased in LSc skin tissue in vivo. The transfection of specific inhibitor for miR-196a into normal cultured human dermal fibroblasts led to the up-regulation of type 1 collagen protein in vitro. Furthermore, the serum levels of miR-196a were significantly decreased in LSc patients. CONCLUSION: Down-regulation of miR-196a and subsequent overexpression of type 1 collagen in dermal fibroblasts may play a key role in the pathogenesis of LSc. The serum levels of miR-196a may be useful as a diagnostic marker of LSc.
Assuntos
MicroRNAs/metabolismo , Esclerodermia Localizada/genética , Esclerodermia Localizada/metabolismo , Pele/metabolismo , Células Cultivadas , Colágeno Tipo I/metabolismo , Regulação para Baixo , Fibroblastos/metabolismo , Humanos , MicroRNAs/sangue , Reação em Cadeia da Polimerase em Tempo Real , Regulação para CimaAssuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Imunoglobulina G/metabolismo , Psoríase/imunologia , Psoríase/terapia , Idoso , Humanos , Hidronefrose/diagnóstico , Hidronefrose/etiologia , Hidronefrose/imunologia , Imunoglobulina G/sangue , Doenças Linfáticas/diagnóstico , Doenças Linfáticas/etiologia , Doenças Linfáticas/imunologia , Masculino , Prednisolona/uso terapêutico , Psoríase/complicações , Fibrose Retroperitoneal/diagnóstico , Fibrose Retroperitoneal/etiologia , Fibrose Retroperitoneal/imunologia , Tomografia Computadorizada por Raios X , UstekinumabRESUMO
Mycobacterium chelonae is a non-tuberculous, rapidly growing mycobacteria and is widely distributed in the natural environment. In the immunocompetent status, localized cutaneous infections such as cellulitis and subcutaneous abscesses commonly occur after traumatic injury. However, disseminated cutaneous infections occur on a background of immunosuppression. Cutaneous M. chelonae infection presents with a variety of skin eruptions. We report a case of disseminated M. chelonae infection mimicking cutaneous vasculitis. The patient was treated with long-term oral corticosteroids and injected etanercept for the treatment of rheumatoid arthritis and asthma. Because the skin eruptions were preceded by asthma and rheumatoid arthritis and the pathological findings showed fibrinoid necrosis around the vascular of dermis, cutaneous vasculitis was first suspected. The culture from the pus revealed the bacterium which grew within 5 days on Ogawa's culture medium suggesting a rapidly growing mycobacteria. This bacterium was identified as M. chelonae by the DNA-DNA hybridization method. We chose 800 mg/day clarithromycin and 500 mg/day levofloxacin as a result of the drug-sensitivity test. After 6 months of the treatment, infection symptoms disappeared. Rapidly growing mycobacteria should be considered in the differential diagnosis of infections in patients under immunosuppression caused by diseases or drugs such as corticosteroids and biologic agents. Repeated bacterial examinations are important and required for the diagnosis of rapidly growing mycobacteria.
Assuntos
Infecções por Mycobacterium não Tuberculosas/diagnóstico , Mycobacterium chelonae , Dermatopatias Bacterianas/diagnóstico , Antibacterianos/uso terapêutico , Claritromicina/uso terapêutico , Diagnóstico Diferencial , Feminino , Humanos , Hospedeiro Imunocomprometido , Levofloxacino/uso terapêutico , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Dermatopatias Bacterianas/tratamento farmacológico , Vasculite/diagnósticoAssuntos
Fístula Cutânea/cirurgia , Tratamento de Ferimentos com Pressão Negativa , Escleroderma Sistêmico/cirurgia , Transplante de Pele , Úlcera Cutânea/cirurgia , Idoso , Fístula Cutânea/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Escleroderma Sistêmico/complicações , Úlcera Cutânea/etiologia , Resultado do TratamentoRESUMO
Psoriasis and psoriatic arthritis are chronic inflammatory diseases of the skin and joints, but the relationship between them has not been fully understood. Since the delay of treatment for psoriatic arthritis can result in the severe deformities, it is important to identify the pathological triggers of the arthritis. On the other hand, many reports suggest that the changes of immune balance during pre/postpartum period are associated with the state of autoimmune diseases. Here, we report a female case with psoriasis whose arthritis may be triggered by the delivery. Our report suggests that immune tolerance may diminish in the postpartum period, which may alter the susceptibility to arthritis. Female patients should be followed-up carefully during postpartum period against the development of arthritis.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Artrite Psoriásica/patologia , Cuidado Pós-Natal/métodos , Psoríase/patologia , Adulto , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/etiologia , Proteína C-Reativa/metabolismo , Feminino , Técnicas Histológicas , Humanos , Infliximab , Japão , Contagem de Leucócitos , Psoríase/complicações , Psoríase/tratamento farmacológico , Cintilografia , Medronato de Tecnécio Tc 99m , Resultado do TratamentoRESUMO
Objective diagnostic markers have not been in clinical use for psoriasis. In this study, we investigated the levels of miR-424 in hair roots and hair shafts in psoriatic patients, and evaluated the possibility that miR-424 can be a biomarker of the disease. A single hair root and five pieces of hair shafts (~5 cm in length) were obtained from the non-lesional occiput of each individual of 26 psoriatic patients. Control hair samples were collected from nine normal subjects. Samples from 10 atopic dermatitis patients were also included as the disease control. miR-424 levels were determined by quantitative real-time polymerase chain reaction. Hair shaft miR-424 levels were significantly upregulated only in patients with psoriasis compared with normal controls and those with atopic dermatitis. By receiver-operator curve analysis of hair shaft miR-424 to distinguish psoriatic patients from normal subjects, the area under the curve was 0.77. However, relative miR-424 levels were not correlated with disease activity markers including disease duration, body surface area and Psoriasis Area and Severity Index. Hair root miR-424 was not useful for evaluating both diagnosis and severity of the disease. Our results indicated hair shaft miR-424 levels may be useful as a diagnostic marker of psoriasis.
Assuntos
Cabelo/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Psoríase/genética , Psoríase/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Biomarcadores/metabolismo , Estudos de Casos e Controles , Dermatite Atópica/genética , Dermatite Atópica/metabolismo , Feminino , Cabelo/patologia , Humanos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Psoríase/diagnóstico , Adulto JovemAssuntos
MicroRNAs/sangue , Psoríase/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Lupus erythematosus profundus is a rare inflammatory disorder of subcutaneous fat in patients with lupus ery-thematosus. Previous reports suggested that plasmacytoid dendritic cells, which expressed CD123 and CD303 antigens, play a central proinflammatory role in the patho-genesis of lupus erythematosus. To find the factors that determine the response to treatment, we analysed 23 skin specimens from the patients with lupus erythematosus profundus. The patients with considerable lymphocytic inflammation with high percentages of CD123+ cells in dermis and subcutaneous fat significantly responded to the systemic corticosteroid therapies. On the other hand, the patients with minor lymphocytic inflammation with low percentages of CD123+ cells showed poor response to treatments. The mean percentage of CD123+ cells in patients who showed good response to therapy was significantly higher than those that showed poor response (p = 0.027). These results suggest that the clinical response to treatment of lupus erythematosus profundus could be predicted from the histological features.
Assuntos
Glucocorticoides/uso terapêutico , Subunidade alfa de Receptor de Interleucina-3/metabolismo , Linfócitos/patologia , Paniculite de Lúpus Eritematoso/tratamento farmacológico , Paniculite de Lúpus Eritematoso/patologia , Adolescente , Adulto , Criança , Derme/metabolismo , Derme/patologia , Feminino , Técnica Direta de Fluorescência para Anticorpo , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Paniculite de Lúpus Eritematoso/metabolismo , Gordura Subcutânea/metabolismo , Gordura Subcutânea/patologia , Adulto JovemRESUMO
BACKGROUND: Toxic epidermal necrolysis (TEN) is a severe drug-induced cutaneous reaction. Although one of the primary histologic features of TEN is keratinocyte apoptosis, its exact mechanism remains unknown. OBJECTIVES: We investigated the role of microRNAs (miRNAs) in the pathogenesis of severe drug eruptions and evaluated the possibility that miRNA can be a disease marker. METHODS: miRNAs were extracted from tissues and sera of patients. PCR array analyses were performed to identify pathogenic miRNAs. The results were confirmed with quantitative real-time PCR, in situ hybridization, transient transfection of small interfering RNAs or miRNA mimics into cultured keratinocytes, flow cytometry, immunoblotting, luciferase assay, and immunohistochemistry. RESULTS: PCR array analysis and real-time PCR using tissue miRNAs demonstrated that the miR-18a-5p level was increased in the skin of patients with TEN in vivo. Transfection of the miR-18a-5p mimic into keratinocytes in vitro resulted in increased apoptotic cell numbers and caspase-9 activity, which were also increased in the skin of patients with TEN. The miR-18a-5p mimic also downregulated the expression of B-cell lymphoma/leukemia-2-like protein 10 (BCL2L10), an anti-intrinsic apoptotic molecule. A luciferase assay with the BCL2L10 3' untranslated region showed BCL2L10 is directly targeted by miR-18a-5p. The protein and mRNA expressions of BCL2L10 were decreased in the skin of patients with TEN. Transfection with BCL2L10 small interfering RNA induced keratinocyte apoptosis and caspase activity. Furthermore, serum miR-18a-5p levels tended to be increased in patients with TEN and were correlated with areas of skin erythema or erosion in patients with drug eruptions. CONCLUSIONS: Our results indicated that downregulated BCL2L10 caused by miR-18a-5p overexpression mediates intrinsic keratinocyte apoptosis in patients with TEN. Serum miR-18a-5p levels can be a useful disease marker for drug eruptions.
Assuntos
Regulação da Expressão Gênica , MicroRNAs/genética , Síndrome de Stevens-Johnson/genética , Apoptose/genética , Biomarcadores , Perfilação da Expressão Gênica , Predisposição Genética para Doença , Humanos , Queratinócitos/metabolismo , MicroRNAs/sangue , Proteínas Proto-Oncogênicas c-bcl-2/genética , Pele/patologia , Síndrome de Stevens-Johnson/patologiaRESUMO
BACKGROUND: Objective biomarkers that reflect the diagnosis and disease activity have not been in clinical use for psoriasis. OBJECTIVES: We investigated the hair root miR-19a levels, regulatory microRNA of TNF-α, and evaluated the possibility that miR-19a can be a biomarker of psoriasis. MATERIALS AND METHODS: microRNAs were extracted from hair roots of patients with psoriasis (n = 18) and healthy controls (n = 22). Samples from 10 atopic dermatitis patients and 4 dermatomyositis patients were also included as the disease controls. miR-19a levels were determined by quantitative real-time PCR. RESULTS: Hair root levels of miR-19a were significantly up-regulated only in psoriasis compared with normal controls. In characteristics (ROC) curve analysis for hair root miR-19a, to distinguish psoriasis patients from normal subjects, the areas under curve (AUC) was 0.87. Relative miR-19a levels were inversely and significantly correlated with duration between symptom onset and the first visit to the hospital in psoriasis patients. CONCLUSIONS: Our results indicated hair root miR-19a levels are effective as a disease marker.
Assuntos
Cabelo/metabolismo , MicroRNAs/metabolismo , Psoríase/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores/metabolismo , Humanos , Pessoa de Meia-Idade , Curva ROC , Índice de Gravidade de Doença , Regulação para Cima , Adulto JovemRESUMO
In the present study, we evaluated the possibility that we can utilize hair shaft miR-29a levels as disease marker of scleroderma. Hair samples were obtained from 20 scleroderma patients, five dermatomyositis patients and 13 controls. microRNAs were purified from hairs as well as skins or sera, and miR-29a levels were measured with quantitative real-time polymerase chain reaction. Mean hair miR-29a levels in scleroderma patients were significantly lower than those in control subjects or dermatomyositis, while expression levels of hair shaft marker keratin 34 were similar among them. There was no strong correlation among the miR-29a levels in the hair, skin and serum of each patient, suggesting that hair microRNAs can be independent biomarkers. We found scleroderma patients with decreased miR-29a levels had contracture of the phalanges at a significantly higher prevalence than those without. To confirm the clinical usefulness of hair microRNAs, large-scale researches are needed in the future.