Shoichiro Ohta

Kyoto University, Kioto, Kyōto, Japan

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Publications (50)182.79 Total impact

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    ABSTRACT: Although it is currently recognized that bronchial asthma is not a single disease but a syndrome, we have not yet made use of our new understanding of this heterogeneity as we treat asthma patients. To increase the efficacy of anti-asthma drugs and to decrease costs, it is important to stratify asthma patients into subgroups and to develop therapeutic strategies for each subgroup. Periostin has recently emerged as a biomarker for bronchial asthma, unique in that it is useful not in diagnosis but in categorizing asthma patients. We first found that periostin is a novel component of subepithelial fibrosis in bronchial asthma downstream of IL-13 signals. Thereafter, it was shown that periostin can be a surrogate biomarker of type 2 immune responses, the basis of the notion that a detection system of serum periostin is potentially a companion diagnostic for type 2 antagonists. Furthermore, we have recently shown that serum periostin can predict resistance or hyporesponsiveness to inhaled corticosteroids, based on its contribution to tissue remodeling or fibrosis in bronchial asthma. Thus, serum periostin has two characteristics as a biomarker for bronchial asthma: it is both a surrogate biomarker of type 2 immune responses and a biomarker reflecting tissue remodeling or fibrosis. We can take advantage of these characteristics to develop stratified medicine in bronchial asthma.
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    Allergology International 05/2015; 63(3). DOI:10.1016/j.alit.2015.04.001
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    ABSTRACT: Asthma is a heterogeneous disease composed of various phenotypes. Periostin, a molecule inducible with interleukin (IL)-4 or IL-13 in bronchial epithelial cells, is a biomarker of "TH2-high" asthma. The objective of this study is to examine whether the serum periostin concentrations are correlated with the severity, specific phenotype(s), or comorbidity of asthma. Serum concentrations of periostin were measured in 190 Japanese asthmatic patients and 11 healthy controls. The protocol was registered under UMIN 000002980 in the clinical trial registry. The serum concentrations of periostin were significantly higher (P = 0.014) in asthmatics [70.0 (54.0-93.5) ng/ml] than in healthy subjects [57.0 (39.0-63.0) ng/ml], though we found no correlation between serum periostin concentrations and treatment steps required to control asthma. To characterize "high-periostin" phenotype(s), the patients with asthma were divided among tertiles based on the serum concentrations of periostin. The high-periostin group was older at onset of asthma (P = 0.04), had a higher prevalence of aspirin intolerance (P = 0.04) or concomitant nasal disorders (P = 0.03-0.001), higher peripheral eosinophil counts (P < 0.001), and lower pulmonary function (P = 0.02-0.07). The serum concentrations of periostin were particularly high in asthmatic patients complicated by chronic rhinosinusitis with nasal polyps and olfactory dysfunction. In contrast, neither atopic status, control status of asthma, nor quality of life were related with the "high-periostin" phenotype. Elevated periostin concentrations in serum were correlated with a specific phenotype of eosinophilic asthma, late-onset and often complicated by obstructive pulmonary dysfunction and nasal disorders. Copyright © 2014 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.
    Allergology International 04/2015; 18(2). DOI:10.1016/j.alit.2014.07.003
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    Allergology International 02/2015; 63(2). DOI:10.1016/j.alit.2015.01.001
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    ABSTRACT: Epidermal hyperplasia is a histological hallmark observed in both atopic dermatitis (AD) and psoriasis, although the clinical features and the underlying immunological disorders of these diseases are different. We previously showed that periostin, a matricellular protein, plays a critical role in epidermal hyperplasia in AD, using a mouse model and a 3-dimensional organotypic coculture system. In this study, we explore the hypothesis that periostin is involved in epidermal hyperplasia in psoriasis.
    Allergology International 01/2015; 64(1-1):41-48. DOI:10.1016/j.alit.2014.06.001
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    ABSTRACT: KL-6 and surfactant proteins A and D are the only established serum biomarkers of idiopathic pulmonary fibrosis (IPF). We have previously shown that serum levels of periostin, a unique matricellular protein, are elevated and correlated with pulmonary function in patients with IPF. We sought to determine whether the serum periostin levels correlate with overall survival (OS) and time-to-event (TTE), as a parameter reflecting long-term outcome, and with the extent of abnormality on chest high-resolution computed tomography (HRCT) scores in patients with IPF. Twenty-nine patients with IPF were analyzed retrospectively. The mean observation period was 1035.2±663.1 days (range, 112-1800 days). High-resolution computed tomography (HRCT) scores were calculated based on the extent of abnormality evidenced by HRCT. We evaluated if there were any correlations between the serum periostin levels and clinical parameters, including HRCT score, using Spearman׳s rank correlation coefficients and analyzed predictors of OS and TTE using the log-rank tests. We showed that the serum periostin levels significantly correlated with the increase of honeycombing score on HRCT during a 6-month period. Log-rank tests showed that a higher serum periostin level was a predictor of a shortened OS and TTE. Greater extents of fibrotic lesions on HRCT scan were predictors of shortened OS and TTE. In IPF patients, the serum periostin level may be a good predictive biomarker for an increase in the radiological fibrotic area and long-term outcome. Copyright © 2014 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.
    01/2015; 53(2). DOI:10.1016/j.resinv.2014.12.003
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    ABSTRACT: Tissue injury promotes metastasis of several human cancers, although factors associated with wound healing that attract circulating tumor cells have remained unknown. Here, we examined the primary and metastatic lesions that appeared 1 month after trauma in a patient with acral lentiginous melanoma. The levels of mRNA for periostin (POSTN), type 1 collagen, and fibronectin were significantly increased in the metastatic lesion relative to the primary lesion. The increase of these extracellular matrix proteins at the wound site was reproduced in a mouse model of wound healing, with the upregulation of Postn mRNA persisting the longest. POSTN was expressed in the region surrounding melanoma cell nests in metastatic lesions of both wounded mice and the patient. POSTN attenuated the cell adhesion and promoted the migration of melanoma cells without affecting their proliferation in vitro. In the mouse model, the wound site as well as subcutaneously injected osteoblasts that secrete large amounts of POSTN invited the metastasis of remotely-transplanted melanoma cells on the sites. Osteoblasts with suppression of POSTN by shRNA showed a greatly reduced ability to promote such metastasis. Our results suggest that POSTN is a key factor in promoting melanoma cell metastasis to wound sites by providing a premetastatic niche.
    PLoS ONE 01/2015; 10(6):e0129704. DOI:10.1371/journal.pone.0129704 · 3.53 Impact Factor
  • American Journal of Respiratory and Critical Care Medicine 12/2014; 190(12):1449-52. DOI:10.1164/rccm.201407-1290LE · 11.99 Impact Factor
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    ABSTRACT: Background Recent studies recommend periostin as a systemic biomarker of eosinophilic airway inflammation to predict responses to novel treatments that targets eosinophilic TH2-driven inflammation in asthmatic patients. Objective To investigate the clinical implications of serum periostin levels in patients with aspirin-exacerbated respiratory disease (AERD) based on its overlapping TH2-mediated pathogenesis with the eosinophilic asthma. Methods Serum periostin levels were measured by human periostin enzyme-linked immunosorbent assay (ELISA) in serum samples from 277 adults with asthma. Serum periostin levels were compared between patients with AERD and aspirin tolerant asthma (ATA) with other asthma phenotypes, such as severe or nonsevere asthma and eosinophilic or noneosinophilic asthma. The association of serum periostin levels with clinical parameters (including disease severity and comorbid condition) was analyzed. Results Serum periostin levels were significantly higher in patients with AERD vs ATA, patients with severe asthma vs nonsevere asthma, and patients with eosinophilic asthma vs noneosinophilic asthma (P=.005, P=.02, and P=.001, respectively). Multivariate regression analysis revealed serum periostin levels as a significant parameter to predict AERD phenotype (P=.006) together with severe asthma phenotype (P=.04). In addition, serum periostin levels correlated with blood eosinophil counts (Spearman ñ = 0.244, P<.001) and sputum eosinophil counts (Spearman ñ = 0.261, P < 0.001). Higher serum periostin levels were noted in comorbid AERD patients with more severe chronic rhinosinusitis (Lund-Mackay stages 3 and 4) than those with less severe chronic rhinosinusitis (Lund-Mackay stages 1 and 2) (P = .03). Conclusion Serum periostin levels are significantly elevated in AERD patients and associated with AERD phenotype and disease severity.
    Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 09/2014; 113(3). DOI:10.1016/j.anai.2014.06.014 · 2.75 Impact Factor
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    American Journal of Respiratory and Critical Care Medicine 08/2014; 190(4):472-4. DOI:10.1164/rccm.201403-0562LE · 11.99 Impact Factor
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    ABSTRACT: In steroid-naive patients with asthma, several gene variants are associated with a short-term response to inhaled corticosteroid (ICS) treatment; this has mostly been observed in Caucasians. However, not many studies have been conducted for other ethnicities. Here, we aimed to determine the relationship between the annual decline in forced expiratory flow volume in one second (FEV1 ) and the variant of the glucocorticoid-induced transcript 1 gene (GLCCI1) in Japanese patients with asthma receiving long-term ICS treatment, taking into account the effect of high serum periostin levels, a known association factor of pulmonary function decline and a marker of refractory eosinophilic/Th2 inflammation. In this study, 224 patients with asthma receiving ICS treatment for at least 4 years were enrolled. The effects of single-nucleotide polymorphisms (SNPs) in GLCCI1, stress-induced phosphoprotein 1 (STIP1), and T gene on the decline in FEV1 of 30 ml/year or greater were determined. Besides the known contributing factors, that is, the most intensive treatment step, ex-smoking, and high serum periostin levels (≥95 ng/ml), the GG genotype of GLCCI1 rs37973, and not other SNPs, was independently associated with a decline in FEV1 of 30 ml/year or greater. When patients were stratified according to their serum periostin levels, the GG genotype of rs37973 was significantly associated with blood eosinophilia (≥250/μl) in the high serum periostin group. A GLCCI1 variant is a risk factor of pulmonary function decline in Japanese patients with asthma receiving long-term ICS treatment. Thus, GLCCI1 may be associated with response to ICS across ethnicities.
    Allergy 03/2014; DOI:10.1111/all.12400 · 6.00 Impact Factor
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    ABSTRACT: Periostin, an extracellular matrix protein belonging to the fasciclin family, has been shown to play a critical role in the process of remodeling during tissue/organ development or repair. Periostin functions as a matricellular protein in cell activation by binding to their receptors on cell surface, thereby exerting its biological activities. After we found that periostin is a downstream molecule of interleukin (IL)-4 and IL-13, signature cytokines of type 2 immune responses, we showed that periostin is a component of subepithelial fibrosis in bronchial asthma, the first formal proof that periostin is involved in allergic inflammation. Subsequently, a great deal of evidence has accumulated demonstrating the significance of periostin in allergic inflammation. It is of note that in skin tissues, periostin is critical for amplification and persistence of allergic inflammation by communicating between fibroblasts and keratinocytes. Furthermore, periostin has been applied to development of novel diagnostics or therapeutic agents for allergic diseases. Serum periostin can reflect local production of periostin in inflamed lesions induced by Th2-type immune responses and also can predict the efficacy of Th2 antagonists against bronchial asthma. Blocking the interaction between periostin and its receptor, αv integrin, or down-regulating the periostin expression shows improvement of periostin-induced inflammation in mouse models or in in vitro systems. It is hoped that diagnostics or therapeutic agents targeting periostin will be of practical use in the near future.
    Allergology International 03/2014; 63(2). DOI:10.2332/allergolint.13-RAI-0663
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    ABSTRACT: Background Recent findings indicate that periostin, an extracellular matrix protein induced by T helper 2 cytokines, plays a critical role in the pathogenesis of atopic dermatitis (AD). Objectives To determine whether serum periostin level is associated with clinical phenotype in adult patients with AD. Methods An enzyme-linked immunosorbent assay was performed to determine serum periostin levels in 257 adult patients with AD, 66 patients with psoriasis vulgaris (PV) as a disease control and 25 healthy controls. Serum periostin levels were analysed together with clinical characteristics and laboratory parameters, including thymus and activation-regulated chemokine (TARC), lactate dehydrogenase (LDH), blood eosinophil count and total IgE. Immunohistochemical analysis evaluated the expression of periostin in association with various clinical phenotypes of AD. The effect of treatment on serum periostin level was also assessed. Results Serum periostin was significantly higher in patients with AD than in patients with PV and healthy controls. Periostin level was found to be positively correlated with disease severity, TARC level, LDH level and eosinophil count, but not with IgE level. Higher serum periostin level was observed in patients with extrinsic AD compared with patients with intrinsic AD; the positive correlation of disease severity disappeared in patients with intrinsic AD. Robust expression of periostin was detected in the dermis of patients with AD with erythroderma, lichenification and, to a lesser extent, scaly erythema. Serial measurement of serum periostin revealed decreased levels of periostin after treatment for AD. Conclusions Periostin may play a critical role in disease severity and chronicity in the pathogenesis of AD.
    British Journal of Dermatology 03/2014; 171(2). DOI:10.1111/bjd.12943 · 4.10 Impact Factor
  • The Journal of allergy and clinical immunology 02/2014; 133(5). DOI:10.1016/j.jaci.2013.12.1084 · 11.25 Impact Factor
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    ABSTRACT: Proliferation and differentiation of keratinocytes are normally well balanced, but this balance can be perturbed in wound healing and is dysregulated in pathological conditions such as atopic dermatitis. Epithelial-mesenchymal interaction affects this event via the cross-talk of cytokines and growth factors. Periostin, a matricellular protein, has an important role during reepithelialization in wound healing and is critical for hyperproliferation of keratinocytes in atopic dermatitis. Here we investigated how periostin regulates proliferation and differentiation of keratinocytes in the epithelial-mesenchymal interactions using a three-dimensional organotypic air-liquid interface coculture system. The release of IL-1α from keratinocytes and subsequent IL-6 production from fibroblasts were critical for keratinocyte proliferation and differentiation. Periostin secreted from fibroblasts was required for IL-1α-induced IL-6 production and enhanced IL-6 production by activation of the NF-κB pathway synergistically with IL-1α. Thus, the combination of an autocrine loop of periostin and a paracrine loop composed of IL-1α and IL-6 regulates keratinocyte proliferation and differentiation in the epithelial-mesenchymal interactions, and periostin tunes the magnitude of keratinocyte proliferation and differentiation by interacting with the paracrine IL-1α/IL-6 loop.Journal of Investigative Dermatology advance online publication, 19 December 2013; doi:10.1038/jid.2013.500.
    Journal of Investigative Dermatology 11/2013; DOI:10.1038/jid.2013.500 · 6.37 Impact Factor
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    ABSTRACT: Biomarkers are generally important for the treatment of patients from the points of diagnosis of disease, assessment of cure, assessment of prognosis such as metastasis or recurrence, prevention of disease, and prediction of drug efficacy. Currently it is well accepted that allergic diseases such as bronchial asthma and atopic dermatitis are not single diseases, but syndromes encompassing different diseases entities. Therefore, it is important to cluster allergic disease patients to assess prognosis or the choice of therapeutic drugs, and useful biomarkers are required for these purposes. Periostin, an extracellular matrix protein, has recently emerged as a biomarker useful for clustering asthma patients. We further found that periostin plays an important role in allergic inflammation and based on this finding we are now developing therapeutic agents targeting periostin against allergic diseases. Since periostin is involved in the pathogenesis of various inflammatory diseases in addition to allergic diseases, such diagnostics and therapeutic agents can be applied to many inflammatory diseases. In this article, we describe the history of periostin research and our application of basic research to the development of diagnostics and therapeutic agents against inflammatory diseases.
    Rinsho byori. The Japanese journal of clinical pathology 10/2013; 61(10):900-8.
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    ABSTRACT: Periostin, an extracellular matrix protein, contributes to subepithelial thickening in asthmatic airways, and its serum levels reflect airway eosinophilic inflammation. However, the relationship between periostin and the development of airflow limitation, a functional consequence of airway remodeling, remains unknown. We aimed to determine the relationship between serum periostin levels and pulmonary function decline in asthmatic patients on inhaled corticosteroid (ICS) treatment. Two hundred twenty-four asthmatic patients (average age, 62.3 years) treated with ICS for at least 4 years were enrolled. Annual changes in FEV1, from at least 1 year after the initiation of ICS treatment to the time of enrollment or later (average, 16.2 measurements over 8 years per individual), were assessed. At enrollment, clinical indices, biomarkers that included serum periostin, and periostin gene polymorphisms were examined. Associations between clinical indices or biomarkers and a decline in FEV1 of 30 mL or greater per year were analyzed. High serum periostin levels (≥95 ng/mL) at enrollment, the highest treatment step, higher ICS daily doses, a history of admission due to asthma exacerbation, comorbid or a history of sinusitis, and ex-smoking were associated with a decline in FEV1 of 30 mL or greater per year. Multivariate analysis showed that high serum periostin, the highest treatment step, and ex-smoking were independent risk factors for the decline. Polymorphisms of periostin gene were related to higher serum periostin levels (rs3829365) and a decline in FEV1 of 30 mL or greater per year (rs9603226). Serum periostin appears to be a useful biomarker for the development of airflow limitation in asthmatic patients on ICS.
    The Journal of allergy and clinical immunology 06/2013; 132(2). DOI:10.1016/j.jaci.2013.04.050 · 11.25 Impact Factor
  • Shoichiro Ohta, Kenji Izuhara
    Arerugī = [Allergy] 06/2013; 62(6):652-64.
  • Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 05/2013; 110(5):387-8. DOI:10.1016/j.anai.2013.01.024 · 2.75 Impact Factor
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    ABSTRACT: To diagnose atopic dermatitis (AD), an appearance of eczema examined by experienced dermatologists is required. Therefore, biomarkers to diagnose AD or to reflect the severity of AD would be of a great use for non-specialists in the clinic or hospitals. We can apply such a biomarker for realization of personalized medicine for AD in the future. Interleukin-4 (IL-4) and IL-13 have been known to play important roles in the pathogenesis of allergic diseases including AD. In addition to these, we previously identified SCCA1, SCCA2, and periostin as IL-4/IL-13-inducible genes. We recently established ELISA systems to measure serum levels of SCCA1, SCCA2, and periostin and evaluated their usefulness in the treatment of AD patients. Serum SCCA1 and SCCA2 are up-regulated in AD patients and can distinguish AD patients from non-atopic controls, and their serum levels reflect eczema grades. Periostin concentration is also elevated in the serum of AD patients. These results demonstrate that SCCA1, SCCA2, and periostin might be promising biomarkers for personalized medicine in allergic diseases including AD.
    Rinsho byori. The Japanese journal of clinical pathology 03/2013; 61(3):247-55.