Role of CTGF on podocytes and tubulointerstitium in chronic kidney disease.

CTGF 对慢性肾脏病足细胞和肾小管间质的作用。

• 批准号: 21790806
• 负责人: YOKOI Hideki
• 金额: $ 2.75万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21790806/
• 关键词: 腎臓学; CTGF; Cre; ポドサイト; loxP; 慢性腎臓病; nephrin; 細胞外基質; TGF-beta; 細胞外基

CTGF is a growth factor strongly induced by TGF-β and has a profibrotic effects. Neonatal death of CTGF knockout mice by the deformity of the ribs makes the evaluation of the role of CTGF in chronic kidney disease difficult. To solve these problems, we constructed CTGF floxed mice. We generated systemic inducible CTGF knockdown mice and podocyte-specific CTGF knockout mice to investigate the role of CTGF in chronic kidney disease.1. Systemic tamoxifen inducible CTGF knockdown mice.We crossed RosaCreER^<T2> mice, which activate Cre recombinase by the stimulation of tamoxifen, with CTGF floxed mice to generate systemic inducible CTGF knockdown mice. Although expression of CTGF in the kidney, liver and heart of systemic inducible CTGF knockdown mice is reduced by 80-90%, histological examination showed normal phenotype. Gene array were performed to find candidate gene on the CTGF-downstream pathway.2. Diabetic nephropathy in podocyte-specific CTGF knockout mice.We generated podocyte-specific CTGF knockout mice. Although expression of CTGF mRNA in glomeruli was decreased by 87%, the kidney was normal and urinary albumin excretion was within normal range. Next, we generated type 1 diabetic mice by injection of streptozotocin in podocyte-specific CTGF knockout mice. There is no significant difference between diabetic wild-type mice and diabetic podocyte-specific CTGF knockout mice in urinary albumin excretion and renal histology.

CTGF是一种由TGF-β强烈诱导的生长因子，具有促纤维化作用。CTGF基因敲除小鼠的新生儿因肋骨畸形而死亡，使得CTGF在慢性肾脏疾病中的作用难以评估。为了解决这些问题，我们构建了CTGF floxed小鼠。我们建立了系统性诱导CTGF敲除小鼠和足细胞特异性CTGF敲除小鼠来研究CTGF在慢性肾脏疾病中的作用.全身性他莫昔芬诱导的CTGF敲低小鼠：我们将<T2>通过他莫昔芬刺激激活Cre重组酶的RosaCreER+小鼠与CTGF敲低小鼠杂交以产生全身性诱导的CTGF敲低小鼠。尽管全身性诱导CTGF敲低小鼠的肾脏、肝脏和心脏中CTGF的表达降低了80- 90%，但组织学检查显示正常表型。采用基因芯片技术寻找CTGF下游通路的候选基因.足细胞特异性CTGF敲除小鼠中的糖尿病肾病：我们产生足细胞特异性CTGF敲除小鼠。尽管肾小球CTGF mRNA表达降低87%，但肾脏正常，尿白蛋白排泄在正常范围内。接下来，我们通过在足细胞特异性CTGF敲除小鼠中注射链脲佐菌素来产生1型糖尿病小鼠。糖尿病野生型小鼠和糖尿病足细胞特异性CTGF敲除小鼠在尿白蛋白排泄和肾脏组织学方面没有显著差异。

项目成果

Podocyte-specific expression of tamoxifen-inducible Cre recombinase in mice

• DOI: 10.1093/ndt/gfq029
• 发表时间: 2010-07-01
• 期刊: NEPHROLOGY DIALYSIS TRANSPLANTATION
• 影响因子: 6.1
• 作者: Yokoi, Hideki;Kasahara, Masato;Nakao, Kazuwa
• 通讯作者: Nakao, Kazuwa

Podocyte-specific expression of tsmoxifen-inducible Cre recombinase in mice

小鼠中tsmoxifen诱导型Cre重组酶的足细胞特异性表达

• 发表时间: 2010
• 作者: Yokoi H.;他8名
• 通讯作者: 他8名

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Reduction in urinary excretion of neutrophil gelatinase-associated lipocalin by angiotensin receptor blockers in hypertensive patients.

高血压患者中血管紧张素受体阻滞剂可减少中性粒细胞明胶酶相关脂质运载蛋白的尿排泄。

• 发表时间: 2009
• 期刊: Nephrol Dial Transplant 24
• 作者: Kasahara M;Mori K;Satoh N;Kuwabara T;Yokoi H;Shimatsu A;Sugawara A;Mukoyama M;Nakao K.
• 通讯作者: Nakao K.

タモキシフェン誘導性糸球体上皮細胞特異的Cre過剰発現マウスの作成

他莫昔芬诱导的肾小球上皮细胞特异性 Cre 过表达小鼠的创建

• 发表时间: 2010
• 作者: 横井秀基;笠原正登;森潔;小川喜久;〓原孝成;齋藤陽子;今牧博貴;川西智子;古賀健一;石井輝;菅原照;向山政志;中尾一和
• 通讯作者: 中尾一和