BIOCHEMICAL AND HISTOCHEMICAL EXAMINATIONS ON LIPJD-BINDING PROTEINS (LBP), PEROXISOME PROLIFERATOR ACTIVATED RECEPTORS (PPAR) AND RETINOL RECEPTORS (RXR) IN KIDNEY.

肾脏中 LIPJD 结合蛋白 (LBP)、过氧化物酶体增殖物激活受体 (PPAR) 和视黄醇受体 (RXR) 的生化和组织化学检查。

• 批准号: 12671034
• 负责人: KIMURA Hideki
• 金额: $ 2.18万
• 依托单位: FACULTY OF MEDICINE FUKUI MEDICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671034/
• 关键词: kidnev; PPAR; Hold-binding nrotein; cell culture; PAI- 1; GETP; eosmophil; homocvsteine; Immuno histochemistry; Macrophage; Homocysteine

1. Investigation on the expression ofLBPs and PPARs in normal and diseased human kidneys.(1) In normal human kidney, liver type (L-) fatty acid-binding protein (FABP) and heart-type FABP were predominantly localized in cytoplasm of proximal and distal renal tubular epithelial cells (RTEC), respectively. PPAR-α was mainly present in cytoplasm of proximal RTEC and PPAR-γ was present in cytoplasm of distal RTEC and collecting ducts.(2) As for transplanted kidneys suffering from severe hypoxia, the expressions of L-FABP and PPAR-α were increased in cytoplasm of some proximal RTECs. In interstitial nephritis, nuclear stainings for L-FABP and PPAR-α were found in some proximal RTECs, suggesting the interaction between L-FABP and PPAR-α. Purified L-FABP contained endogenously long-chain fatty acids which can serve as ligands, stimulators for PPAR-α. In interstitial nephritis, PPAR-α was expressed in infiltrating eosinophils but not macrophages. In membranous nephropathy, nuclear staining for … More PPAR-α was more frequent than normal kidney.2. Investigation on the expression of LBPs and PPARs in human cultured proximal renal tubular epithelial cells.(1) Indirect immunofluorescence method and immunoblotting revealed that L-FABP and PPAR-α were expressed in human cultured proximal renal tubular epithelial cells. PAI-1 was also expressed in the cultured cells.(2) PAI-1 antigen was detected in the medium of human cultured proximal renal tubular cells at a concentration of 250-600 ng/mL after the cells were cultured in the medium including several growth factors and bioactive molecules. Addition of hydrocortisone and epinephrine to the basic medium increased the concentration of PAI- 1 in the conditioned medium of the cultured cells. Hypoxia appeared to induce further the expression of PAI-1 in the cells cultured in the growth medium.3. Analysis of relationships between clinical variables and advanced renal disease and vascular disease.In hemodialysis patients with high HDL-C status, cholesteryl ester transfer protein (CETP) was a protective factor against vascular disease. A common C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene was associated with increased serum levels of homocysteine which causes oxidative stress to endothelial cells. The homozygous mutants (TT genotype) were younger at the induction of hemodialysis and had a shorter duration of dialysis, suggesting that hyperhomocysteinemia may be related to accelerated progression of renal damage and mortality after initiation of dialysis. Among diabetic patients, PAI-1 concentrations in urine were higher in those with severe proteinuria over 1000 mg/gCr than those with microalbuminuria, while plasma PAI-1 levels were unchanged during progression of diabetic nephropathy. Urinary PAI-1 levels were positively associated with urinary NAG and sugar levels. Less

1. LBP和PPARs在正常和病变肾脏中表达的研究(1)在正常人肾脏，肝型（L-）脂肪酸结合蛋白（FABP）和心脏型FABP主要定位于近端和远端肾小管上皮细胞（RTEC）的细胞质中，分别。PPAR-α主要表达于近端RTEC的胞浆中，PPAR-γ主要表达于远端RTEC和集合管的胞浆中。(2)重度缺氧时，移植肾近端部分RTEC胞浆中L-FABP和PPAR-α表达增加。在间质性肾炎中，在一些近端RTEC中发现L-FABP和PPAR-α的核染色，表明L-FABP和PPAR-α之间存在相互作用。纯化的L-FABP含有内源性长链脂肪酸，可作为PPAR-α的配体和刺激物。在间质性肾炎中，PPAR-α表达于浸润性嗜酸性粒细胞而非巨噬细胞。在膜性肾病中， ...更多信息 PPAR-α阳性率高于正常肾脏.人近端肾小管上皮细胞LBP和PPARs表达的研究(1)间接免疫荧光法和免疫印迹法显示，L-FABP和PPAR-α在培养的人近端肾小管上皮细胞中均有表达。派-1在培养的细胞中也有表达。(2)在含有多种生长因子和生物活性分子的培养液中培养人近端肾小管细胞后，在培养液中检测到浓度为250-600 ng/mL的派-1抗原。基础培养基中添加氢化可的松和肾上腺素可增加培养细胞条件培养基中派- 1的浓度。缺氧可进一步诱导细胞派-1的表达.临床变量与晚期肾脏疾病和血管疾病的关系分析在高HDL-C状态的血液透析患者中，胆固醇酯转移蛋白（CETP）是血管疾病的保护因素。亚甲基四氢叶酸还原酶（MTHFR）基因中常见的C677 T突变与血清同型半胱氨酸水平升高相关，同型半胱氨酸水平升高导致内皮细胞氧化应激。纯合子突变体（TT基因型）在诱导血液透析时更年轻，透析持续时间更短，这表明高同型半胱氨酸血症可能与开始透析后肾损伤和死亡率的加速进展有关。在糖尿病患者中，尿中派-1浓度在重度蛋白尿超过1000 mg/gCr的患者中高于微量白蛋白尿的患者，而血浆派-1水平在糖尿病肾病进展过程中无变化。尿派-1水平与尿NAG和血糖水平正相关。少

项目成果

Tsukahara H.: "Methylenetetrahydrofolate reductase polymorphismin Kawasaki disease"Pediat. Int.. 742. 236-240 (2001)

Tsukahara H.：“川崎病中的亚甲基四氢叶酸还原酶多态性”Pediat。

Kimura H: "Cholesteryl ester transfer protein as a protective factor against vascular disease in hemodialysis patients"Am. J. Kidney Dis.. (2001)

Kimura H：“胆固醇酯转移蛋白作为血液透析患者血管疾病的保护因子”Am。

Kimura H: "AC677T mutation in the methylenetetrahydrofolate reductase gene modifies serum cysteine in dialysis patients"Am. J. Kidney Dis.. 36. 925-933 (2000)

Kimura H：“亚甲基四氢叶酸还原酶基因中的 AC677T 突变会改变透析患者的血清半胱氨酸”Am。

Tsukahara H: "Methylenetetrahydrofolate reductase polymorphism in Kawasaki disease"Pediat. Int.. 42. 236-240 (2000)

Tsukahara H：“川崎病中的亚甲基四氢叶酸还原酶多态性”Pediat。

Kimura H.: "A C677T mutation in the methylenetetrahydrofolatereductase gene modifies serum cysteine in dialysis patients"Am. J. Kidney Dis.. 36. 925-933 (2000)

Kimura H.：“亚甲基四氢叶酸还原酶基因中的 C677T 突变会改变透析患者的血清半胱氨酸”Am。