A role of BMP on the development of glomerular capillary tufts

BMP 对肾小球毛细血管簇发育的作用

• 批准号: 23591202
• 负责人: MIYAZAKI Yoichi
• 金额: $ 2.91万
• 依托单位: Jikei University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591202/
• 关键词: Noggin; podocyte; proximal tubule; cross-talk; nephron; BMP; ネフロン; 細胞間クロストーク; MMP; VEGF; Diabetic nephropathy

We established the transgenic mouse line (Podocine-rtTA; TetO-Noggin), in which Noggin, Bmp inhibitor, was selectively expressed only in the podocytes under the control of Dox. We then analyzed the adult transgenic mice with or without Dox for 3 months. Podocine-rtTA; TetO-Noggin with Dox showed a reduced expression of TG-lectin expression in proximal tubules, interstitial edema and a decrease in proximal tubular cells positive for phosphorylated Smad1/5/8. In contrast, the morphology of glomerulus appeared normal. It has been shown that BMP7-receptor, but not BMP per se, is not expressed in proximal tubules. Conditional knockout of Bmp7 in podoccytes has been reported to lead to a defect in proximal tubule development during embryonic stage. In conjunction with these findings, we assume that, in adulthood also, the podocyte injury cause not only the development of glomerulosclerosis, but also a damage in proximal tubules via a decrease of BMP expression.

我们建立了转基因小鼠系（Podocine-rtTA；TetO-Noggin），其中Bmp抑制剂Noggin仅在Dox控制下的足细胞中选择性表达。然后我们对使用或不使用 Dox 的成年转基因小鼠进行了 3 个月的分析。 Podocine-rtTA； TetO-Noggin 与 Dox 显示近端肾小管中 TG-凝集素表达降低、间质性水肿以及磷酸化 Smad1/5/8 阳性近端肾小管细胞减少。相反，肾小球的形态显得正常。已表明，BMP7 受体（而非 BMP 本身）在近曲小管中不表达。据报道，足细胞中 Bmp7 的条件性敲除会导致胚胎阶段近端小管发育缺陷。结合这些发现，我们假设，在成年期，足细胞损伤不仅会导致肾小球硬化症的发生，还会通过 BMP 表达的减少而导致近端肾小管损伤。

项目成果

Mice are unable to endogenously regenerate podocytes during the repair of immunotoxin-induced glomerular injury

小鼠在免疫毒素诱导的肾小球损伤修复过程中无法内源性再生足细胞

• 发表时间: 2014
• 期刊: Nephrol Dial Transplant
• 作者: Miyazaki Y;Shimizu A;Ichikawa I;Hosoya T;Pastan I;Matsusaka T
• 通讯作者: Matsusaka T

Mice are unable to endogenously regenerate podocytes during the repair of immunotoxin-induced glomerular injury.

小鼠在免疫毒素诱导的肾小球损伤修复过程中无法内源性再生足细胞。

• 发表时间: 2014
• 期刊: Nephrol Dial Transplant
• 作者: Miyazaki Y;Shimizu A;Ichikawa I;Hosoya T;Pastan I;Matsusaka T.
• 通讯作者: Matsusaka T.

Keap1 inhibition attenuates glomerulosclerosis

• DOI: 10.1093/ndt/gfu002
• 发表时间: 2014-04-01
• 期刊: NEPHROLOGY DIALYSIS TRANSPLANTATION
• 影响因子: 6.1
• 作者: Miyazaki, Yoichi;Shimizu, Akihiro;Matsusaka, Taiji
• 通讯作者: Matsusaka, Taiji

Foxc1 Gene Null Mutation Causes Ectopic Budding and Kidney Hypoplasia but Not Dysplasia

• DOI: 10.1159/000351291
• 发表时间: 2013-01-01
• 期刊: CELLS TISSUES ORGANS
• 影响因子: 2.7
• 作者: Komaki, Fumiyo;Miyazaki, Yoichi;Motojima, Masaru
• 通讯作者: Motojima, Masaru

Keap1-Nrf2経路と糖尿病性腎症

Keap1-Nrf2通路与糖尿病肾病

• 发表时间: 2012
• 作者: 清水昭博;松阪泰二;宮崎陽一;細谷龍男;宮田敏男;山本雅之
• 通讯作者: 山本雅之