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Obesity-induced Vitamin D Deficiency Contributes to Lung Fibrosis and Airway Hyperresponsiveness
DC Field | Value | Language |
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dc.contributor.author | 김성렬 | - |
dc.contributor.author | 박경희 | - |
dc.contributor.author | 박중원 | - |
dc.contributor.author | 박혜정 | - |
dc.contributor.author | 이재현 | - |
dc.contributor.author | 정숙인 | - |
dc.date.accessioned | 2021-12-28T16:48:39Z | - |
dc.date.available | 2021-12-28T16:48:39Z | - |
dc.date.issued | 2021-03 | - |
dc.identifier.issn | 1044-1549 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/186807 | - |
dc.description.abstract | Vitamin D (VitD) has pleiotropic effects. VitD deficiency is closely involved with obesity and may contribute to the development of lung fibrosis and aggravation of airway hyperresponsiveness (AHR). We evaluated the causal relationship between VitD deficiency and the lung pathologies associated with obesity. In vivo effects of VitD supplementation were analyzed using high-fat diet (HFD)-induced obese mice and TGF-β1 (transforming growth factor-β1) triple transgenic mice. Effects of VitD supplementation were also evaluated in both BEAS-2B and primary lung cells from the transgenic mice. Obese mice had decreased 25-OH VitD and VitD receptor expressions with increases of insulin resistance, renin and angiotensin-2 system (RAS) activity, and leptin. In addition, lung pathologies such as a modest increase in macrophages, enhanced TGF-β1, IL-1β, and IL-6 expression, lung fibrosis, and AHR were found. VitD supplementation to HFD-induced obese mice recovered these findings. TGF-β1-overexpressing transgenic mice enhanced macrophages in BAL fluid, lung expression of RAS, epithelial-mesenchymal transition markers, AHR, and lung fibrosis. VitD supplementation also attenuated these findings in addition to the attenuation of the expressions of TGF-β1, and phosphorylated Smad-2/3 in lung. Supplementing in vitro-stimulated BEAS-2B and primary lung cells with VitD inhibited TGF-β1 expression, supporting the suppressive effect of VitD for TGF-β1 expression. These results suggest that obesity leads to VitD deficiency and worsens insulin resistance while enhancing the expression of leptin, RAS, TGF-β1, and proinflammatory cytokines. These changes may contribute to the development of lung fibrosis and AHR. VitD supplementation rescues these changes and may have therapeutic potential for asthma with obesity. | - |
dc.description.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | American Thoracic Society | - |
dc.relation.isPartOf | AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Biomarkers / metabolism | - |
dc.subject.MESH | Body Weight / drug effects | - |
dc.subject.MESH | Cells, Cultured | - |
dc.subject.MESH | Cytokines / metabolism | - |
dc.subject.MESH | Diet, High-Fat | - |
dc.subject.MESH | Dietary Supplements | - |
dc.subject.MESH | Epithelial-Mesenchymal Transition / drug effects | - |
dc.subject.MESH | Glucose Tolerance Test | - |
dc.subject.MESH | Inflammation / pathology | - |
dc.subject.MESH | Insulin / metabolism | - |
dc.subject.MESH | Leptin / blood | - |
dc.subject.MESH | Lung / metabolism | - |
dc.subject.MESH | Lung / pathology | - |
dc.subject.MESH | Male | - |
dc.subject.MESH | Methacholine Chloride | - |
dc.subject.MESH | Mice, Inbred C57BL | - |
dc.subject.MESH | Mice, Transgenic | - |
dc.subject.MESH | Obesity / blood | - |
dc.subject.MESH | Obesity / complications* | - |
dc.subject.MESH | Pulmonary Fibrosis / blood | - |
dc.subject.MESH | Pulmonary Fibrosis / etiology* | - |
dc.subject.MESH | Receptors, Calcitriol / metabolism | - |
dc.subject.MESH | Renin / blood | - |
dc.subject.MESH | Renin-Angiotensin System / drug effects | - |
dc.subject.MESH | Respiratory Hypersensitivity / blood | - |
dc.subject.MESH | Respiratory Hypersensitivity / etiology* | - |
dc.subject.MESH | Transforming Growth Factor beta1 / metabolism | - |
dc.subject.MESH | Vitamin D / analogs & derivatives | - |
dc.subject.MESH | Vitamin D / blood | - |
dc.subject.MESH | Vitamin D / pharmacology | - |
dc.subject.MESH | Vitamin D Deficiency / blood | - |
dc.subject.MESH | Vitamin D Deficiency / etiology* | - |
dc.title | Obesity-induced Vitamin D Deficiency Contributes to Lung Fibrosis and Airway Hyperresponsiveness | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.googleauthor | Heejae Han | - |
dc.contributor.googleauthor | Sook In Chung | - |
dc.contributor.googleauthor | Hye Jung Park | - |
dc.contributor.googleauthor | Eun Yi Oh | - |
dc.contributor.googleauthor | Sung-Ryeol Kim | - |
dc.contributor.googleauthor | Kyung Hee Park | - |
dc.contributor.googleauthor | Jae-Hyun Lee | - |
dc.contributor.googleauthor | Jung-Won Park | - |
dc.identifier.doi | 10.1165/rcmb.2020-0086OC | - |
dc.contributor.localId | A00566 | - |
dc.contributor.localId | A01427 | - |
dc.contributor.localId | A01681 | - |
dc.contributor.localId | A01769 | - |
dc.contributor.localId | A03086 | - |
dc.relation.journalcode | J00113 | - |
dc.identifier.eissn | 1535-4989 | - |
dc.identifier.pmid | 33296297 | - |
dc.identifier.url | https://www.atsjournals.org/doi/10.1165/rcmb.2020-0086OC | - |
dc.subject.keyword | asthma | - |
dc.subject.keyword | lung fibrosis | - |
dc.subject.keyword | obesity | - |
dc.subject.keyword | transforming growth factor-β1 | - |
dc.subject.keyword | vitamin D | - |
dc.contributor.alternativeName | Kim, Sung Ryeol | - |
dc.contributor.affiliatedAuthor | 김성렬 | - |
dc.contributor.affiliatedAuthor | 박경희 | - |
dc.contributor.affiliatedAuthor | 박중원 | - |
dc.contributor.affiliatedAuthor | 박혜정 | - |
dc.contributor.affiliatedAuthor | 이재현 | - |
dc.citation.volume | 64 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 357 | - |
dc.citation.endPage | 367 | - |
dc.identifier.bibliographicCitation | AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, Vol.64(3) : 357-367, 2021-03 | - |
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