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| 1.
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論文
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Hara, Akinori ; Furuichi, Kengo ; Koshino, Akihiko ; Yasuda, Haruka ; Tran, Trang Thi Thu ; Iwata, Yasunori ; Sakai, Norihiko ; Shimizu, Miho ; Kaneko, Shuichi ; Nakamura, Hiroyuki ; Wada, Takashi ; 原, 章規 ; 古市, 賢吾 ; 岩田, 恭宜 ; 坂井, 宣彦 ; 清水, 美保 ; 金子, 周一 ; 中村, 裕之 ; 和田, 隆志
概要:
金沢大学医薬保健研究域医学系<br />Introduction: We examined the impact of autoantibodies on the erythropoietin receptor (EPOR) in type
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2 diabetic patients with chronic kidney disease (CKD). Methods: A total of 112 Japanese patients with type 2 diabetes who had CKD were enrolled in this study and followed for a mean of 45 months. Sera from these patients were screened for anti-EPOR antibodies using enzyme-linked immunosorbent assays. Results: Anti-EPOR antibodies were detected in 26 patients (23%). Anti-EPOR antibodies were associated with low hemoglobin concentrations and decreased renal function. In patients with biopsy-proven diabetic nephropathy, anti-EPOR antibodies were associated with increased levels of interstitial inflammation. A decrease in renal function was observed more frequently in patients with antibodies than in those without antibodies, and the presence of the antibodies together with well-known clinical parameters, including proteinuria and low glomerular filtration rate, was a significant risk factor for end-stage renal disease. In human tubular epithelial HK-2 cells, IgG fractions containing anti-EPOR antibodies upregulated the expression of monocyte chemoattractant protein-1 mRNA under a high concentration of glucose. Conclusion: Anti-EPOR antibodies might be involved in the progression of renal lesions and in the impaired erythropoiesis in type 2 diabetic patients with CKD. Furthermore, the presence of anti-EPOR antibodies may be an additional predictor for end-stage renal disease in type 2 diabetes. © 2017 International Society of Nephrology<br />Embargo Period 12 months
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| 2.
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坂井, 宣彦 ; Sakai, Norihiko
概要:
取得学位：博士(医学), 学位授与番号：医博甲第1475号, 学位授与年月日：平成13年3月31日,学位授与年：2001
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| 3.
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論文
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坂井, 宣彦
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金沢大学医第1内科<br />ヒト半月体形成性腎炎の発症・進展における,p38MAPKリン酸化を介した活性型NF-κB及びMIP-1a発現の意義と,ラット実験半月体形成性腎炎モデルにおけるp38MAPKリン酸化抑制効果を検討した.その結果,
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ヒト半月体形成性腎炎において免疫組織学的にp-p38MAPK及び活性型NF-κB発現を糸球体半月体形成細胞細胞核に確認した.更にその他の実験により半月体形成性腎炎の発症・進展にp38MAPKリン酸化を介した活性型NF-κB及びMIP-1a発現の重要性が示され,加えてp38MAPKリン酸化制御が半月体形成性腎炎の新しい治療標的分子となり得ることが示唆された<br />原著論文
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| 4.
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論文
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坂井, 宣彦
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第11回 金沢大学十全医学賞受賞論文
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北島, 信治 ; 遠山, 直志 ; 原, 章規 ; 岩田, 恭宜 ; 坂井, 宣彦 ; 清水, 美保 ; 古市, 賢吾 ; 和田, 隆志
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| 6.
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論文
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坂井, 宣彦 ; 遠山, 直志 ; 岩田, 恭宣 ; 清水, 美保 ; 古市, 賢吾 ; 今村, 龍 ; 須田, 貴司 ; 金子, 周一 ; 和田, 隆志
概要:
金沢大学医薬保健研究域医学系<br />Mortality from infections has been reported to be higher in hemodialysis (HD) patients. Although dys
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function of neutrophils against bacterial infection was reported in HD patients, the precise mechanism remains to be clarified. We therefore examined the impacts of neutrophil inflammatory signaling on bactericidal activity in HD patients. Comprehensive analyses of intracellular signalings were performed in whole blood of HD patients and control using a microarray system. To confirm the contribution of the signaling to bactericidal activity in neutrophils, we examined the phosphorylation, bacterial killing function, reactive oxygen species (ROS) production, and myeloperoxidase (MPO) release in neutrophils against Staphylococcus aureus. RNA microarray analysis showed the suppression of p38 mitogen activated protein kinase (MAPK) signaling in HD patients. Neutrophils in HD patients showed the impairment of bactericidal activity against S. aureus compared to healthy subjects. Phosphorylation rate of p38MAPK of neutrophils in response to S. aureus was lower in HD patients than healthy subjects. The levels of ROS produced by neutrophils after co-culture with S. aureus were lower in HD patients, on the other hand, there was no difference of MPO release between HD patients and healthy subjects. A selective pharmacological inhibitor of p38MAPK suppressed bacterial killing function as well as ROS production in neutrophils of healthy subjects. Impairment of p38MAPK signaling pathway might contribute to the suppression of neutrophil bactericidal activity in HD patients through less production of ROS. © 2018 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.<br />Embargo Period 12 months
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| 7.
論文 |
論文
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坂井, 宣彦 ; Sakai, Norihiko
概要:
金沢大学附属病院血液浄化療法部<br />線維化は臓器障害に対する過度の創傷治癒反応，すなわち細胞外基質沈着と細胞外基質産生能を有する細胞の集積を特徴とする．しかし，これら過度の創傷治癒反応をもたらす分子生物学的基盤は完全には同定されていな
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い．本研究では、これら過度の創傷治癒反応をもたらす分子生物学的基盤として、脂質メディエーターの一つであるリゾフォスファチジン酸(LPA）およびその受容体LPA1シグナルに着目し、上皮間葉連関を介した臓器線維化にはたす意義の解明を試みた。その結果、尿細管上皮細胞でのLPA-LPA1シグナルが線維芽細胞の増殖や分化を誘導することで、腎線維化進展に寄与することを明らかにし、この知見を論文化した。<br />Ｆibrosis is charactereized by the expansion of the fibroblast pool, but the mechanisms driving it remain to be fully clarified. We found that lysophosphatidic acid (LPA) and its receptor (LPA1) signaling drives fibroblast proliferation and activation during the development of renal fibrosis by inducing connective tissue growth factor (CTGF). Unilateral ureteral obstruction (UUO)-induced increases in renal collagen were significantly attenuated in LPA1-deficient mice (LPA1-/-) as compared to LPA1-sufficient mice (LPA+/+), as was the accumulations of fibroblasts. CTGF was detected mainly in tubular epithelial cells, and its levels were suppressed in LPA1-/-. LPA-LPA1 signaling directly induced CTGF expression by primary proximal tubular epithelial cells (PTECs). PTEC-derived CTGF mediated renal fibroblast proliferation and myofibroblast differentiation. These results suggest that targeting LPA-LPA1 signaling could be a therapeutic strategy for renal fibrosis.<br />研究課題/領域番号:26461218, 研究期間(年度):2014-04-01 - 2017-03-31
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| 8.
論文 |
論文
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坂井, 宣彦 ; Sakai, Norihiko
概要:
金沢大学附属病院血液浄化療法部<br />線維化は臓器障害に対する過度の創傷治癒反応、すなわち細胞外基質沈着と細胞外基質産生能を有する細胞の集積を特徴とする。近年、末期腎不全の予備軍として慢性腎臓病(CKD)が注目されている。このCKDが進
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展し腎不全に至る過程において、各種腎疾患は腎間質線維化という共通のプロセスをとることを特徴とする。本研究では、細胞骨格依存性シグナルが、腎固有細胞の生物学的特性を調節することで腎間質線維化にはたす意義の解明を試みた。その結果、腎固有細胞でのTGF-bシグナルによる細胞骨格依存性シグナルが、筋線維芽細胞分化を誘導することで、腎間質線維化進展に寄与することを明らかにした。<br />Fibrosis is characterized by an excessive wound healing response to organ damage, causing extracellular matrix deposition and accumulation of fibroblasts/myofibroblasts. Recently, chronic kidney disease (CKD) has been thought as being at risk of developing end-stage renal disease. In the process of CKD progression to renal failure, various renal diseases are characterized by taking a common process which is renal interstitial fibrosis. In this study, we attempted to elucidate the significance of cytoskeleton-dependent signals for renal interstitial fibrosis by regulating the biological properties of renal resident cells. As a result, it was revealed that the cytoskeleton-dependent signal by TGF-b1 in renal resident cells contributes to the progression of renal interstitial fibrosis by inducing myofibroblast differentiation.<br />研究課題/領域番号:17K09691, 研究期間(年度):2017-04-01 - 2020-03-31<br />出典：「細胞骨格依存性シグナルの腎線維化にはたす意義」研究成果報告書 課題番号17K09691（KAKEN：科学研究費助成事業データベース（国立情報学研究所））（https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-17K09691/17K09691seika/)を加工して作成
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