{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1360004237628529152.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1371/journal.pone.0202842"}},{"identifier":{"@type":"URI","@value":"http://dx.plos.org/10.1371/journal.pone.0202842"}},{"identifier":{"@type":"PMID","@value":"30986278"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@value":"Role of the high-affinity leukotriene B4 receptor signaling in fibrosis after unilateral ureteral obstruction in mice"}],"description":[{"notation":[{"@value":"Leukotriene B4 (LTB4) is a lipid mediator that acts as a potent chemoattractant for inflammatory leukocytes. Kidney fibrosis is caused by migrating inflammatory cells and kidney-resident cells. Here, we examined the role of the high-affinity LTB4 receptor BLT1 during development of kidney fibrosis induced by unilateral ureteral obstruction (UUO) in wild-type (WT) mice and BLT1 knockout (BLT1-/-) mice. We found elevated expression of 5-lipoxygenase (5-LOX), which generates LTB4, in the renal tubules of UUO kidneys from WT mice and BLT1-/- mice. Accumulation of immunoreactive type I collagen in WT UUO kidneys increased over time; however, the increase was less prominent in BLT1-/- UUO kidneys. Accumulation of S100A4-positive fibroblasts increased temporally in WT UUO kidneys, but was again less pronounced in-BLT1-/- UUO kidneys. The same was true of mRNA encoding transforming growth factor-β (TGF)-β and fibroblast growth factor (FGF)-2. Finally, accumulation of F4/80-positive macrophages, which secrete TGF-β, increased temporally in WT UUO and BLT1-/- UUO kidneys, but to a lesser extent in the latter. Following LTB4 stimulation in vitro, macrophages showed increased expression of mRNA encoding TGF-β/FGF-2 and Col1a1, whereas L929 fibroblasts showed increased expression of mRNA encoding α smooth muscle actin (SMA). Bone marrow (BM) transplantation studies revealed that the area positive for type I collagen was significantly smaller in BLT1-/-BM→WT than in WT-BM→WT. Thus, LTB4-BLT1 signaling plays a critical role in fibrosis in UUO kidneys by increasing accumulation of macrophages and fibroblasts. Therefore, blocking BLT1 may prevent renal fibrosis."}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380004237628529036","@type":"Researcher","foaf:name":[{"@value":"Mariko Kamata"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004237628529285","@type":"Researcher","foaf:name":[{"@value":"Hideki Amano"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004237628529288","@type":"Researcher","foaf:name":[{"@value":"Yoshiya Ito"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004237628529032","@type":"Researcher","foaf:name":[{"@value":"Tomoe Fujita"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004237628529025","@type":"Researcher","foaf:name":[{"@value":"Fumisato Otaka"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004237628529291","@type":"Researcher","foaf:name":[{"@value":"Kanako Hosono"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004237628529538","@type":"Researcher","foaf:name":[{"@value":"Kouju Kamata"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004237628529416","@type":"Researcher","foaf:name":[{"@value":"Yasuo Takeuchi"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004237628529292","@type":"Researcher","foaf:name":[{"@value":"Takehiko Yokomizo"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004237628529037","@type":"Researcher","foaf:name":[{"@value":"Takao Shimizu"}]},{"@id":"https://cir.nii.ac.jp/crid/1420001326234576896","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"70181641"},{"@type":"NRID","@value":"1000070181641"},{"@type":"NRID","@value":"9000001646671"},{"@type":"NRID","@value":"9000259836007"},{"@type":"NRID","@value":"9000000400401"},{"@type":"NRID","@value":"9000283603956"},{"@type":"NRID","@value":"9000356588084"},{"@type":"NRID","@value":"9000283604056"},{"@type":"NRID","@value":"9000319068786"},{"@type":"NRID","@value":"9000021377969"},{"@type":"NRID","@value":"9000259835852"},{"@type":"NRID","@value":"9000388493730"},{"@type":"NRID","@value":"9000001824824"},{"@type":"NRID","@value":"9000020380428"},{"@type":"NRID","@value":"9000259835859"},{"@type":"NRID","@value":"9000283603863"},{"@type":"NRID","@value":"9000014197032"},{"@type":"NRID","@value":"9000020524373"},{"@type":"NRID","@value":"9000001766929"},{"@type":"NRID","@value":"9000309185816"},{"@type":"NRID","@value":"9000347361111"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/mmajima"}],"foaf:name":[{"@value":"Masataka Majima"}]}],"contributor":[{"@id":"https://cir.nii.ac.jp/crid/1380004237628529544","@type":"Researcher","foaf:name":[{"@value":"Jean-Claude Dussaule"}],"role":"editor"}],"publication":{"publicationIdentifier":[{"@type":"EISSN","@value":"19326203"}],"prism:publicationName":[{"@value":"PLOS ONE"}],"dc:publisher":[{"@value":"Public Library of Science (PLoS)"}],"prism:publicationDate":"2019-02-28","prism:volume":"14","prism:number":"2","prism:startingPage":"e0202842"},"reviewed":"false","dcterms:accessRights":"http://purl.org/coar/access_right/c_abf2","dc:rights":["http://creativecommons.org/licenses/by/4.0/"],"url":[{"@id":"http://dx.plos.org/10.1371/journal.pone.0202842"}],"createdAt":"2019-02-28","modifiedAt":"2022-09-12","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Male","dc:title":"Male"},{"@id":"https://cir.nii.ac.jp/all?q=Mice,%20Knockout","dc:title":"Mice, Knockout"},{"@id":"https://cir.nii.ac.jp/all?q=Science","dc:title":"Science"},{"@id":"https://cir.nii.ac.jp/all?q=Macrophages","dc:title":"Macrophages"},{"@id":"https://cir.nii.ac.jp/all?q=Q","dc:title":"Q"},{"@id":"https://cir.nii.ac.jp/all?q=R","dc:title":"R"},{"@id":"https://cir.nii.ac.jp/all?q=Receptors,%20Leukotriene%20B4","dc:title":"Receptors, Leukotriene B4"},{"@id":"https://cir.nii.ac.jp/all?q=Apoptosis","dc:title":"Apoptosis"},{"@id":"https://cir.nii.ac.jp/all?q=Fibroblasts","dc:title":"Fibroblasts"},{"@id":"https://cir.nii.ac.jp/all?q=Kidney","dc:title":"Kidney"},{"@id":"https://cir.nii.ac.jp/all?q=Fibrosis","dc:title":"Fibrosis"},{"@id":"https://cir.nii.ac.jp/all?q=Mice,%20Inbred%20C57BL","dc:title":"Mice, Inbred C57BL"},{"@id":"https://cir.nii.ac.jp/all?q=Mice","dc:title":"Mice"},{"@id":"https://cir.nii.ac.jp/all?q=Kidney%20Tubules","dc:title":"Kidney Tubules"},{"@id":"https://cir.nii.ac.jp/all?q=Medicine","dc:title":"Medicine"},{"@id":"https://cir.nii.ac.jp/all?q=Animals","dc:title":"Animals"},{"@id":"https://cir.nii.ac.jp/all?q=Kidney%20Diseases","dc:title":"Kidney Diseases"},{"@id":"https://cir.nii.ac.jp/all?q=Research%20Article","dc:title":"Research Article"},{"@id":"https://cir.nii.ac.jp/all?q=Signal%20Transduction","dc:title":"Signal Transduction"},{"@id":"https://cir.nii.ac.jp/all?q=Ureteral%20Obstruction","dc:title":"Ureteral Obstruction"}],"project":[{"@id":"https://cir.nii.ac.jp/crid/1040000781834340096","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"15H05904"},{"@type":"JGN","@value":"JP15H05904"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PLANNED-15H05904/"}],"notation":[{"@language":"ja","@value":"リポクオリティを認識する受容体分子機構"},{"@language":"en","@value":"Receptors that recognize lipoquality"}]},{"@id":"https://cir.nii.ac.jp/crid/1040000782019665536","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"19K09250"},{"@type":"JGN","@value":"JP19K09250"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19K09250/"}],"notation":[{"@language":"ja","@value":"急性下肢循環障害におけるmPGES-1/PGE2の虚血改善メカニズムの解明"},{"@language":"en","@value":"Microsomal Prostaglandin E Synthase-1/PGE2 axis induces recovery from ischemia via recruitment of regulatory Tregs"}]},{"@id":"https://cir.nii.ac.jp/crid/1040282256811053568","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"15H05897"},{"@type":"JGN","@value":"JP15H05897"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-ORGANIZER-15H05897/"}],"notation":[{"@language":"ja","@value":"「リポクオリティ」領域研究の推進"},{"@language":"en","@value":"Steering group for the LipoQuality program project"}]},{"@id":"https://cir.nii.ac.jp/crid/1040282256970022912","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"18H02605"},{"@type":"JGN","@value":"JP18H02605"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18H02605/"}],"notation":[{"@language":"ja","@value":"リンパ管、リンパ組織の可塑性を制御する生理活性脂質の解析と治療応用への基盤研究"},{"@language":"en","@value":"Bioactive lipids as regulators of plasticity of lymphatics"}]},{"@id":"https://cir.nii.ac.jp/crid/1040282256970032256","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"18H02627"},{"@type":"JGN","@value":"JP18H02627"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18H02627/"}],"notation":[{"@language":"ja","@value":"ロイコトリエンB4産生酵素と受容体の疾患モデルにおける役割"},{"@language":"en","@value":"The in vivo roles of biosynthetic enzyme and receptors for leukotriene B4"}]},{"@id":"https://cir.nii.ac.jp/crid/1040285300660818432","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"19KK0199"},{"@type":"JGN","@value":"JP19KK0199"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19KK0199/"}],"notation":[{"@language":"ja","@value":"X線結晶構造解析を基盤としたBLT2作働薬の開発"},{"@language":"en","@value":"Development of BLT2 agonist based on the structure of BLT2"}]}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360002216795061376","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The intrinsic prostaglandin E2–EP4 system of the renal tubular epithelium limits the development of tubulointerstitial fibrosis in mice"}]},{"@id":"https://cir.nii.ac.jp/crid/1360002218658385920","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Sustained-release prostacyclin analog ONO-1301 ameliorates 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YORK"}]},{"@id":"https://cir.nii.ac.jp/crid/1360011146123039616","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Detection of leukotriene B4 in cardiac tissue and its role in infarct extension through leucocyte migration"}]},{"@id":"https://cir.nii.ac.jp/crid/1360017282464595456","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"The leukotriene\n                    <scp>\n                      B\n                      <sub>4</sub>\n                    </scp>\n                    /\n                    <scp>BLT1</scp>\n                    ‐dependent neutrophil accumulation exacerbates immune complex‐mediated glomerulonephritis"}]},{"@id":"https://cir.nii.ac.jp/crid/1360022304970942080","@type":"Article","resourceType":"preprint","relationType":["hasPreprint"],"jpcoar:relatedTitle":[{"@value":"Role of the high-affinity leukotriene B\n                  <sub>4</sub>\n                  receptor signaling in fibrosis after unilateral ureteral obstruction in mice"}]},{"@id":"https://cir.nii.ac.jp/crid/1360283691835617408","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"BLT1 signalling protects the liver against acetaminophen hepatotoxicity by preventing excessive accumulation of hepatic neutrophils"}]},{"@id":"https://cir.nii.ac.jp/crid/1360292619201883648","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Role of the 5-lipooxygenase pathway in obstructive nephropathy"}]},{"@id":"https://cir.nii.ac.jp/crid/1360567185442942336","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Angiotensin<scp>II</scp>subtype 1a receptor signaling in resident hepatic macrophages induces liver metastasis 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760."}]},{"@id":"https://cir.nii.ac.jp/crid/1361137044994022784","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"A pivotal role of cytosolic phospholipase A2 in bleomycin-induced pulmonary fibrosis"}]},{"@id":"https://cir.nii.ac.jp/crid/1361137046294860416","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The leukotriene B4 receptor (BLT) antagonist BIIL284 decreases atherosclerosis in ApoE−/− mice"}]},{"@id":"https://cir.nii.ac.jp/crid/1361418519343170688","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Interstitial fibrosis in obstructive nephropathy"}]},{"@id":"https://cir.nii.ac.jp/crid/1361418520468139008","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Mechanisms of Tubulointerstitial Fibrosis"}]},{"@id":"https://cir.nii.ac.jp/crid/1361418521203283968","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Vascular endothelial growth factor-C and -D are involved in lymphangiogenesis in mouse unilateral ureteral obstruction"}]},{"@id":"https://cir.nii.ac.jp/crid/1361699994601750784","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"CD44 Disruption Prevents Degeneration of the Capillary Network in Obstructive Nephropathy via Reduction of TGF-β1–Induced Apoptosis"}]},{"@id":"https://cir.nii.ac.jp/crid/1361699996192802048","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Constitutive activation of 5-lipoxygenase in the lungs of patients with idiopathic pulmonary fibrosis."}]},{"@id":"https://cir.nii.ac.jp/crid/1361981468741274240","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Obstructive nephropathy: Insights from genetically engineered animals"}]},{"@id":"https://cir.nii.ac.jp/crid/1361981468916292352","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Ureteral obstruction in neonatal mice elicits segment-specific tubular cell responses leading to nephron loss11See Editorial by Woolf, p. 761."}]},{"@id":"https://cir.nii.ac.jp/crid/1361981469077915136","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Absence of Leukotriene B4 Receptor 1 Confers Resistance to Airway Hyperresponsiveness and Th2-Type Immune Responses"}]},{"@id":"https://cir.nii.ac.jp/crid/1361981471221543552","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"A G-protein-coupled receptor for leukotriene B4 that mediates chemotaxis"}]},{"@id":"https://cir.nii.ac.jp/crid/1361981471344098560","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Bone marrow-derived cPLA2α contributes to renal fibrosis progression"}]},{"@id":"https://cir.nii.ac.jp/crid/1362262944064124800","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"TGF‐β signaling and the fibrotic 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way"}]},{"@id":"https://cir.nii.ac.jp/crid/1362544421334398336","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Immunological aspects of acute ureteral obstruction: Immune cell infiltrate in the kidney"}]},{"@id":"https://cir.nii.ac.jp/crid/1362544421383326464","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The role of FGF-2 in renal fibrogenesis"}]},{"@id":"https://cir.nii.ac.jp/crid/1362825893648737152","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Leukotrienes"}]},{"@id":"https://cir.nii.ac.jp/crid/1362825895189623168","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Leukotrienes, LTC4 and LTB4, in bronchoalveolar lavage in bronchial asthma and other respiratory diseases"}]},{"@id":"https://cir.nii.ac.jp/crid/1363107370876657664","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Inhibition site of dexamethasone on 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