記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.kint.2020.03.032

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Kidney ischemia–reperfusion injury is a major cause of acute kidney injury (AKI). Following reduced kidney perfusion, the pathological overproduction of reactive oxygen and reactive nitrogen species play a substantial role in the development of kidney ischemia–reperfusion injury. Arginase 2 (ARG2) competes with nitric oxide synthase for the same substrate, L-arginine, and is implicated in the regulation of reactive nitrogen species. Therefore, we investigated the role of ARG2 in kidney ischemia–reperfusion injury using human proximal tubule cells (HK-2) and a mouse model of kidney ischemia–reperfusion injury. ARG2 was predominantly expressed in kidney tubules of the cortex, which was increased after ischemia–reperfusion injury. In HK-2 cells, ARG2 was expressed in punctate form in the cytoplasm and upregulated after hypoxia–reoxygenation. ARG2 knockdown reduced the level of reactive oxygen species and 3-nitrotyrosine after hypoxia–reoxygenation injury compared with control siRNA. Consistent with these results, in Arg2 knockout mice, abnormal kidney function and the increased acute tubular necrosis score induced by ischemia–reperfusion injury was significantly reduced without any obvious blood pressure changes. Additionally, an accumulation of 3-nitrotyrosine and apoptosis of renal tubule cells were attenuated in Arg2 knockout mice compared with wild-type mice. Inhibition of arginase by Nω-hydroxy-nor-L-arginine alleviated kidney ischemia–reperfusion injury like the results found in Arg2 knockout mice. Thus, ARG2 plays a pivotal role in ischemia–reperfusion-induced AKI by means of nitrosative stress. Hence, an ARG2-specific inhibitor may effectively treat kidney ischemia–reperfusion injury.

DOI： 10.1016/j.kint.2020.03.032

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Genomewide association studies have shown that a nonsynonymous single nucleotide polymorphism in PRKCH is associated with cerebral infarction and atherosclerosis-related complications. We examined the role of PKCη in lipid metabolism and atherosclerosis using apolipoprotein E-deficient (Apoe^−/−) mice. PKCη expression was augmented in the aortas of mice with atherosclerosis and exclusively detected in MOMA2-positive macrophages within atherosclerotic lesions. Prkch^+/+Apoe^−/− and Prkch^−/−Apoe^−/− mice were fed a high-fat diet (HFD), and the dyslipidemia observed in Prkch^+/+Apoe^−/− mice was improved in Prkch^−/−Apoe^−/− mice, with a particular reduction in serum LDL cholesterol and phospholipids. Liver steatosis, which developed in Prkch^+/+Apoe^−/− mice, was improved in Prkch^−/−Apoe^−/− mice, but glucose tolerance, adipose tissue and body weight, and blood pressure were unchanged. Consistent with improvements in LDL cholesterol, atherosclerotic lesions were decreased in HFD-fed Prkch^−/−Apoe^−/− mice. Immunoreactivity against 3-nitrotyrosine in atherosclerotic lesions was dramatically decreased in Prkch^−/−Apoe^−/− mice, accompanied by decreased necrosis and apoptosis in the lesions. ARG2 mRNA and protein levels were significantly increased in Prkch^−/−Apoe^−/− macrophages. These data show that PKCη deficiency improves dyslipidemia and reduces susceptibility to atherosclerosis in Apoe^−/− mice, showing that PKCη plays a role in atherosclerosis development.

DOI： 10.1111/gtc.12402

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Genomewide association studies have shown that a nonsynonymous single nucleotide polymorphism in PRKCH is associated with cerebral infarction and atherosclerosis-related complications. We examined the role of PKCη in lipid metabolism and atherosclerosis using apolipoprotein E-deficient (Apoe-/- ) mice. PKCη expression was augmented in the aortas of mice with atherosclerosis and exclusively detected in MOMA2-positive macrophages within atherosclerotic lesions. Prkch+/+ Apoe-/- and Prkch-/- Apoe-/- mice were fed a high-fat diet (HFD), and the dyslipidemia observed in Prkch+/+ Apoe-/- mice was improved in Prkch-/- Apoe-/- mice, with a particular reduction in serum LDL cholesterol and phospholipids. Liver steatosis, which developed in Prkch+/+ Apoe-/- mice, was improved in Prkch-/- Apoe-/- mice, but glucose tolerance, adipose tissue and body weight, and blood pressure were unchanged. Consistent with improvements in LDL cholesterol, atherosclerotic lesions were decreased in HFD-fed Prkch-/- Apoe-/- mice. Immunoreactivity against 3-nitrotyrosine in atherosclerotic lesions was dramatically decreased in Prkch-/- Apoe-/- mice, accompanied by decreased necrosis and apoptosis in the lesions. ARG2 mRNA and protein levels were significantly increased in Prkch-/- Apoe-/- macrophages. These data show that PKCη deficiency improves dyslipidemia and reduces susceptibility to atherosclerosis in Apoe-/- mice, showing that PKCη plays a role in atherosclerosis development.

DOI： 10.1111/gtc.12402

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/acel.12423

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/nm.3288

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/nm.3288

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/jb/mvi168

記述言語：英語   出版者・発行元：Clinical and Experimental Nephrology  

Background: Encapsulated peritoneal sclerosis (EPS) is a serious complication in patients undergoing peritoneal dialysis (PD). Neutral-pH dialysate is associated with less peritoneal damage and a lower incidence of EPS than conventional PD solution. However, monitoring for peritoneal damage and predicting EPS remain important during PD therapy. Methods: We measured the mesothelial cell area, dialysate-to-plasma ratio of creatinine after 4 h, and concentrations of the potential biological markers effluent fibrin degradation products (eFDPs), cancer antigen-125, and interleukin-6 in the effluent dialysate from patients who had been undergoing PD therapy for > 5 years in our hospital. These biomarkers were obtained from the drainage fluid of the final measurement of peritoneal equilibration testing before withdrawal from PD therapy. The concentrations of these potential biomarkers were measured in 39 patients who withdrew from PD therapy and were enrolled in the study. Results: Three participants developed EPS after withdrawing PD. The dialysate-to-plasma ratio of creatinine, area of mesothelial cells, and interleukin-6 appearance rate in participants who developed EPS tended to be higher than those in patients who did not, but there were no significant differences. Significantly more eFDPs were in participants who developed EPS than in those who did not (138.5 ± 15.1 vs. 32.9 ± 7.4 µg/mL, P = 0.002). There was no difference in the cancer antigen-125 appearance rate between the groups. A cut-off value of eFDPs ≥ 119.1 µg/mL was optimal for predicting EPS (P = 0.006, specificity = 0.972, sensitivity = 1.000). Conclusion: This study shows that eFDPs may be a useful biological marker for predicting EPS in patients undergoing PD using neutral-pH dialysate.

DOI： 10.1007/s10157-024-02565-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Scientific Reports  

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to be renoprotective in ischemia-reperfusion (I/R) injury, with several proposed mechanisms, though additional mechanisms likely exist. This study investigated the impact of luseogliflozin on kidney fibrosis at 48 h and 1 week post I/R injury in C57BL/6 mice. Luseogliflozin attenuated kidney dysfunction and the acute tubular necrosis score on day 2 post I/R injury, and subsequent fibrosis at 1 week, as determined by Sirius red staining. Metabolomics enrichment analysis of I/R-injured kidneys revealed suppression of the glycolytic system and activation of mitochondrial function under treatment with luseogliflozin. Western blotting showed increased nutrient deprivation signaling with elevated phosphorylated AMP-activated protein kinase and Sirtuin-3 in luseogliflozin-treated kidneys. Luseogliflozin-treated kidneys displayed increased protein levels of carnitine palmitoyl transferase 1α and decreased triglyceride deposition, as determined by oil red O staining, suggesting activated fatty acid oxidation. Luseogliflozin prevented the I/R injury-induced reduction in nuclear factor erythroid 2-related factor 2 activity. Western blotting revealed increased glutathione peroxidase 4 and decreased transferrin receptor protein 1 expression. Immunostaining showed reduced 4-hydroxynonenal and malondialdehyde levels, especially in renal tubules, indicating suppressed ferroptosis. Luseogliflozin may protect the kidney from I/R injury by inhibiting ferroptosis through oxidative stress reduction.

DOI： 10.1038/s41598-024-71416-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Arteriosclerosis, Thrombosis, and Vascular Biology  

BACKGROUND: Hyponatremia, frequently observed in patients with chronic kidney disease, is associated with increased cardiovascular morbidity and mortality. Hyponatremia or low osmolality induces oxidative stress and cell death, both of which accelerate vascular calcification (VC), a critical phenotype in patients with chronic kidney disease. Whether hyponatremia or low osmolality plays a role in the pathogenesis of VC is unknown. METHODS: Human vascular smooth muscle cells (VSMCs) and mouse aortic rings were cultured in various osmotic conditions and calcifying medium supplemented with high calcium and phosphate. The effects of low osmolality on phenotypic change and oxidative stress in the cultured VSMCs were examined. Microarray analysis was conducted to determine the main signaling pathway of osmolality-related VC. The transcellular sodium and calcium ions flux across the VSMCs were visualized by live imaging. Furthermore, the effect of osmolality on calciprotein particles (CPPs) was investigated. Associations between arterial intimal calcification and hyponatremia or low osmolality were examined by a cross-sectional study using human autopsy specimens obtained in the Hisayama Study. RESULTS: Low osmolality exacerbated calcification of the ECM (extracellular matrix) of cultured VSMCs and mouse aortic rings. Oxidative stress and osteogenic differentiation of VSMCs were identified as the underlying mechanisms responsible for low osmolality-induced VC. Microarray analysis showed that low osmolality activated the Rac1 (Ras-related C3 botulinum toxin substrate 1)-Akt (protein kinase B) pathway and reduced NCX1 (Na-Ca exchanger 1) expression. Live imaging showed synchronic calcium ion efflux and sodium ion influx via NCX1 when extracellular sodium ion concentrations were increased. An NCX1 inhibitor promoted calcifying media-induced VC by reducing calcium ion efflux. Furthermore, low osmolality accelerated the generation and maturation steps of CPPs. The cross-sectional study of human autopsy specimens showed that hyponatremia and low osmolality were associated with a greater area of arterial intimal calcification. CONCLUSIONS: Hyponatremia and low osmolality promote VC through multiple cellular processes, including the Rac1-Akt pathway activation.

DOI： 10.1161/ATVBAHA.123.320069

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DOI： 10.6084/m9.figshare.26211134

記述言語：英語   出版者・発行元：Nature Publishing Group  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Hypertension Research  

We previously reported that brain atrophy was more severe and progressed more rapidly in patients with end-stage kidney disease on peritoneal dialysis (PD) than those with non-dialysis-dependent chronic kidney disease. However, it remains unknown whether there is a difference between patients on PD and hemodialysis (HD). In total, 73 PD and 34 HD patients who underwent brain magnetic resonance imaging (MRI) were recruited for a cross-sectional analysis. Among them, 42 PD and 25 HD patients who underwent a second brain MRI after 2 years were recruited for a longitudinal analysis. T1-weighted MRI images were analyzed. Total gray matter volume (GMV), total white matter volume, and cerebrospinal fluid volume were segmented, and each volume was quantified using statistical parametric mapping software. The ratio of GMV (GMR) was calculated by dividing GMV by intracranial volume, to adjust for variations in head size. We compared GMR between PD and HD patients in the cross-sectional analysis and the annual change in GMR (AC-GMR) in the longitudinal analysis. In the cross-sectional analysis, age- and sex-adjusted GMR was significantly lower in PD than HD patients [least square mean (LSM): 39.2% vs. 40.0%, P = 0.018]. AC-GMR was significantly greater in PD than HD patients and this difference remained significant even after adjustment for potential confounding factors (LSM: −0.68 vs. −0.28 percentage-points/year, P = 0.011). In conclusion, the present study demonstrated a more rapid progression of brain atrophy in PD patients compared with HD patients. [Figure not available: see fulltext.].

DOI： 10.1038/s41440-023-01530-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Scientific Reports  

Peritoneal calcification is a prominent feature of the later stage of encapsulating peritoneal sclerosis (EPS) in patients undergoing long-term peritoneal dialysis (PD). However, the pathogenesis and preventive strategy for peritoneal calcification remain unclear. Peritoneum samples from EPS patients were examined histologically. Peritoneal calcification was induced in mice by feeding with an adenine-containing diet combined with intraperitoneal administration of lipopolysaccharide and a calcifying solution containing high calcium and phosphate. Excised mouse peritoneum, human mesothelial cells (MeT5A), and mouse embryonic fibroblasts (MEFs) were cultured in calcifying medium. Immunohistochemistry confirmed the appearance of osteoblastic differentiation-marker-positive cells in the visceral peritoneum from EPS patients. Intraperitoneal administration of magnesium suppressed peritoneal fibrosis and calcification in mice. Calcifying medium increased the calcification of cultured mouse peritoneum, which was prevented by magnesium. Calcification of the extracellular matrix was accelerated in Met5A cells and MEFs treated with calcification medium. Calcifying medium also upregulated osteoblastic differentiation markers in MeT5A cells and induced apoptosis in MEFs. Conversely, magnesium supplementation mitigated extracellular matrix calcification and phenotypic transdifferentiation and apoptosis caused by calcifying conditions in cultured MeT5A cells and MEFs. Phosphate loading contributes to the progression of EPS through peritoneal calcification and fibrosis, which can be prevented by magnesium supplementation.

DOI： 10.1038/s41598-023-43657-y

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記述言語：日本語   掲載種別：研究論文（研究会，シンポジウム資料等）   出版者・発行元：(一社)日本腎臓学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Biochemical and Biophysical Research Communications  

Acute kidney injury is an important global health concern as it is associated with high morbidity and mortality. Polyamines, essential for cell growth and proliferation, are known to inhibit cardiovascular disease. However, under conditions of cellular damage, toxic acrolein is produced from polyamines by the enzyme spermine oxidase (SMOX). We used a mouse renal ischemia-reperfusion model and human proximal tubule cells (HK-2) to investigate whether acrolein exacerbates acute kidney injury by renal tubular cell death. Acrolein visualized by acroleinRED was increased in ischemia-reperfusion kidneys, particularly in tubular cells. When HK-2 cells were cultured under 1&#37; oxygen for 24 h, then switched to 21&#37; oxygen for 24 h (hypoxia-reoxygenation), acrolein accumulated and SMOX mRNA and protein levels were increased. Acrolein induced cell death and fibrosis-related TGFB1 mRNA in HK-2 cells. Administration of the acrolein scavenger cysteamine suppressed the acrolein-induced upregulation of TGFB1 mRNA. Cysteamine also inhibited a decrease in the mitochondrial membrane potential observed by MitoTrackerCMXRos, and cell death induced by hypoxia-reoxygenation. The siRNA-mediated knockdown of SMOX also suppressed hypoxia-reoxygenation-induced acrolein accumulation and cell death. Our study suggests that acrolein exacerbates acute kidney injury by promoting tubular cell death during ischemia-reperfusion injury. Treatment to control the accumulation of acrolein might be an effective therapeutic option for renal ischemia-reperfusion injury.

DOI： 10.1016/j.bbrc.2023.05.029

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記述言語：日本語   掲載種別：研究論文（研究会，シンポジウム資料等）   出版者・発行元：(一社)日本腎臓学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Frontiers in Cardiovascular Medicine  

Background: Patients with chronic kidney disease (CKD) have a high risk of left ventricular hypertrophy (LVH). Fibroblast growth factor 23 (FGF23) and indoxyl sulfate (IS) are associated with LVH in patients with CKD, but the interactions between these molecules remain unknown. We investigated whether IS contributes to LVH associated with FGF23 in cultured cardiomyocytes and CKD mice. Methods and results: In cultured rat cardiac myoblast H9c2 cells incubated with IS, mRNA levels of the LVH markers atrial natriuretic factor, brain natriuretic peptide, and β-myosin heavy chain were significantly upregulated. Levels of mRNA of the polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3), which regulates FGF23 O-glycosylation, and FGF23 were also upregulated in H9c2 cells. Intact FGF23 protein expression and fibroblast growth factor receptor 4 (FGFR4) phosphorylation were increased in cell lysates by IS administration. In C57BL/6J mice with heminephrectomy, IS promoted LVH, whereas the inhibition of FGFR4 significantly reduced heart weight and left ventricular wall thickness in IS-treated groups. While there was no significant difference in serum FGF23 concentrations, cardiac FGF23 protein expression was markedly increased in IS-injected mice. GALNT3, hypoxia-inducible factor 1 alpha, and FGF23 protein expression was induced in H9c2 cells by IS treatment and suppressed by the inhibition of Aryl hydrocarbon receptor which is the receptor for IS. Conclusion: This study suggests that IS increases FGF23 protein expression via an increase in GALNT3 and hypoxia-inducible factor 1 alpha expression, and activates FGF23-FGFR4 signaling in cardiomyocytes, leading to LVH.

DOI： 10.3389/fcvm.2023.990422

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： https://doi.org/10.3389/fcvm.2023.990422

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10157-022-02272-3

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一社)日本腎臓学会  

血管内皮細胞と血管平滑筋細胞を用いたin vitro実験系において、腹膜透析液中のグルコース分解物(GDP)が血管新生に及ぼす影響について検討した。ヒト臍帯静脈内皮細胞(HUVEC)とヒト臍帯動脈平滑筋細胞(HUASMC)において、腹膜透析液に含まれる三つの主要なGDPであるメチルグリオキサール(MGO)、3-デオキシグルコソン(3-DG)、5-ヒドロキシメチルフルフラール(5-HMF)の作用を調べた。HUVECとHUASMCはリポポリサッカライド(LPS)で活性化したマウスマクロファージ細胞株の培養上清で刺激した。その結果、HUVECにおいて、血小板由来増殖因子B(PDGFB)のmRNAとタンパク質の発現は、腹膜透析液で観察される濃度のMGO、3-DG、5-HMFへの曝露により低下し、それに続いて分泌されるPDGF受容体βの減少が観察された。HUASMCでは、MGOと5-HMFにより血管内皮増殖因子A(VEGF-A)のmRNAとタンパク質の発現が増加し、5-HMFによりPDGF受容体βの発現が低下した。HUASMCでは、LPS刺激マクロファージの培養上清により、VEGF-Aの発現が亢進し、PDGF受容体βの発現は低下した。以上より、腹膜透析液中のGDPは、血管内皮細胞や血管平滑筋細胞における血管新生因子の不均衡を引き起こし、腹膜における未熟な血管新生を誘導する可能性が示された。

出版者・発行元：Clinical and Experimental Nephrology  

Background: Hypertension is an important prognostic predictor in patients with chronic kidney disease (CKD), and the recommended target blood pressure has been continuously revised. This study aimed to reveal the current antihypertensive practices in Japanese patients with CKD. Methods: In the Fukuoka Kidney disease Registry, we extracted 3664 non-dialysis-dependent patients with CKD. Apparent treatment-resistant hypertension (aTRH) was defined as a failure of blood-pressure control treated with three antihypertensive medication classes or a treatment with ≥ 4 classes regardless of blood pressure. The blood-pressure control complied with the target blood pressure recommended by the KDIGO 2012 guideline. Results: The median age of the patients was 67 years, body mass index (BMI) was 23 kg/m2, and estimated glomerular filtration rate (eGFR) was 40 mL/min/1.73 m2. The number of patients with unachieved blood-pressure control was 1933, of whom 26% received ≥ 3 classes of antihypertensive medications. The first choice of medication was renin–angiotensin system inhibitors, followed by calcium-channel blockers. The rate of thiazide use was low in all CKD stages (3–11%). The prevalence of aTRH was 16%, which was significantly associated with BMI (odds ratio [95% confidence interval] per 1-standard deviation change, 1.38 [1.25–1.53]), decreased eGFR (1.87 [1.57–2.23]), as well as age, diabetes mellitus, and chronic heart disease. Conclusions: Renal dysfunction and obesity are important risk factors of aTRH. Even under nephrologist care, most patients were treated with insufficient antihypertensive medications. It is important to prescribe sufficient classes of antihypertensive medications, including diuretics, and to improve patients’ lifestyle habits.

DOI： 10.1007/s10157-022-02250-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10157-022-02272-3

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00223-022-00947-3

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00223-022-00947-3

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CEN case reports  

Dialysate leakage is one of the causes of peritoneal dialysis (PD)-related peritonitis. The rate of catheter removal in PD-related peritonitis caused by dialysate leakage (PDPDL) is high, and the correct treatment is unclear. We experienced a case of PDPDL that was treated with intravenous and intraperitoneal antibiotic therapy. A 44-year-old Japanese man had high glucose discharge from the exit site after 14 days of initiating PD, and he had a fever and cloudy effluent with a high white cell count. We diagnosed him with PDPDL and began to administer vancomycin and ceftazidime intraperitoneally. However, the peritonitis could not be ameliorated. A culture examination showed Staphylococcus aureus from the effluent of peritoneal cavity and exit site cultures. We began intraperitoneal cefazolin administration according to a drug susceptibility test, but the effluent cell count remained high. As we added intravenous cefazolin administration, his symptoms and cloudy effluent improved, and the effluent cell count normalized. He has not developed any recurrence of dialysate leakage or peritonitis. Our findings suggest that PD-related peritonitis accompanied by other infectious sites, such as PDPDL, should be treated with additional intravenous antibiotic therapy to taking effect on the infectious sites except for peritoneum and to keep plasma concentration of antibiotics sufficient especially in cases with preserved residual kidney function.

DOI： 10.1007/s13730-021-00644-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：シュプリンガー・ジャパン(株)  

症例は44歳男性で、腹膜透析開始14日後にダイアライザー出口部で血糖高値を示し、発熱、透析排液混濁、白血球数増加をきたした。透析液漏出に起因する腹膜透析関連腹膜炎と診断し、バンコマイシン(1g/日)およびセフタジジム(1g/日)の腹腔内投与を開始したが、改善は認められなかった。腹腔内および出口部排液の培養検査にて黄色ブドウ球菌を検出し、薬剤感受性試験をもとにセファゾリン(1.5g/日)腹腔内投与を開始したが、排液細胞数は依然として高値を示した。セファゾリン(1g/日)静脈内投与を追加したところ、症状と排液混濁は改善し、排液細胞数は正常化した。腹膜透析開始2年後も透析液漏出または腹膜炎の再発は認めていない。

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/s41598-021-03551-x

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2169/internalmedicine.6341-20

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10157-020-02018-z

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10157-020-02018-z

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2169/internalmedicine.6341-20

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1159/000512365

記述言語：英語  

DOI： 10.1002/hon.2816

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/s41598-021-03551-x

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/hon.2816

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.bbrc.2020.02.048

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.bbrc.2020.02.048

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2169/internalmedicine.4027-19

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/1744-9987.12865

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/1744-9987.12865

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s13730-019-00421-4

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s13730-018-0371-9

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1371/journal.pone.0213922

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1159/000499401

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1097/MD.0000000000013485

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1097/MD.0000000000013485

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/ndt/gfx305

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/ndt/gfx305

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1371/journal.pone.0196655

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/labinvest.2017.77

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/labinvest.2017.77

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1242/bio.027458

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1242/bio.027458

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1053/j.ajkd.2016.11.026

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1053/j.ajkd.2016.11.026

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/hr.2016.134

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/hr.2016.134

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1172/JCI85647

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/1744-9987.12358

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/1744-9987.12358

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1152/ajprenal.00260.2015

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1152/ajprenal.00260.2015

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/acel.12423

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1152/ajprenal.00669.2014

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/s12882-015-0164-8

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/s12882-015-0164-8

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/dnares/dsv006

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/ki.2014.220

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1152/ajprenal.00669.2014

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/ki.2014.220

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.lfs.2014.07.032

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.lfs.2014.07.032

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/hep.22214

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/hep.22214

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/dnares/12.1.39

開催年月日： 2014年11月

記述言語：英語  

国名：アメリカ合衆国  

開催年月日： 2014年11月

記述言語：英語  

国名：アメリカ合衆国  

開催年月日： 2014年11月

記述言語：英語  

国名：アメリカ合衆国  

開催年月日： 2014年7月

記述言語：日本語  

開催地：パシフィコ横浜   国名：日本国  

【目的】腎線維化の進行に伴いリンパ管が増生することが報告されている．今回我々は，片側尿管結紮(UUO)モデルを用いて，リンパ管新生に関与する血管内皮増殖因子 Vascular endothelial growth factor-C (VEGF-C)の腎線維化への関与について検討した．【方法】7週齢の雄性C57BL6マウスにUUO術を施行し，同時にVEGF-Cを持続投与した群(U+VC群，n=5)と無投与群(U群，n=5)において，リンパ管新生(LYVE-1染色)，間質線維化(Sirius red染色)および線維化関連遺伝子発現(collagen I mRNA,αSMA蛋白)，マクロファージ浸潤(F4/80染色)を比較検討した．【結果】U群では経時的にリンパ管増生，VEGF-R3 mRNA発現亢進，線維化進行、Collagen I mRNA及びαSMA蛋白の発現亢進，マクロファージ浸潤の増加が認められた．一方，U+VC群では，U群に比べ，リンパ管増生の亢進傾向，VEGF-R3蛋白の発現亢進(2.18倍 ,p＜0.05)に伴い，Collagen I mRNA発現の抑制(0.45倍 ,p＜0.05)，αSMA蛋白発現の抑制傾向とともに，間質線維化は軽減(0.53倍, p＜0.01)した．【結論】VEGF-C投与によりリンパ管新生が促進され，腎間質の炎症と線維化が抑制された．

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（指名）  

記述言語：英語   会議種別：シンポジウム・ワークショップ パネル（公募）  

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記述言語：日本語   会議種別：口頭発表（一般）  

記述言語：日本語   会議種別：口頭発表（一般）  

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（指名）  

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記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（指名）  

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（指名）  

記述言語：日本語   会議種別：口頭発表（一般）  

記述言語：日本語   会議種別：口頭発表（一般）  

記述言語：日本語   会議種別：口頭発表（一般）  

記述言語：日本語   会議種別：口頭発表（一般）  

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