Cloning and Functional Analysis of Genes Governing Characteristics of Renal Glomerulus

肾小球特征基因的克隆及功能分析

• 批准号: 09470237
• 负责人: YAMAMOTO Tadashi
• 金额: $ 5.57万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470237/
• 关键词: Glomerulus; Differential screening; Structure-function correlation; Ribonuclease protection assay; In situ hybridization; 構造-機能連間; リポヌクレアーゼプロテクション法; インサイチュ-ハイプリダイゼーション; 糸球体上皮細胞; 遺伝子; ライブラリー; ゴルジ装置; 糸球体腎炎

The unique function of renal glomerulus should be related to its unique structure and molecular components. To understand the structural and functional characteristics of renal glomerulus we first aimed to identify molecules which were specifically present in this structure. We employed differential screening methods to isolate genes which were predominantly expressed in rat glomerulus. Several genes have been isolated as those which were predominantly or uniquely expressed in the glomerulus although their sequences had been registered : olfactomedin-related protein, thymosin β4, heparin-binding epidermal growth factor, VE-cadherin, βCOP and collagen type IV α3 chain. A few novel genes were also isolated as glomerulus-prone ones : 14-1 and 17-3. In addition, several novel genes were identifed as kidney-specific or kidney-prone ones : Ig-Hepta, FR-67 and CS-5. Among them, olfactomedin-related protein and Ig-Hepta were intensively studied. Olfactomedin-related protein was localized in the Golgi apparatus of glomerular podocytes and its C-terminus amino acid sequence, SDEL was a Golgi-retension signal. Ig-Hepta had two Ig-like domains and 7 transmembrane domains. The molecule was immunolocalized in the intercalated cells in the collecting duccts, suggesting a role in acid-base balance regulation.

肾小球的独特功能应与其独特的结构和分子组成有关。为了了解肾小球的结构和功能特征，我们首先旨在识别这种结构中特定存在的分子。我们使用差异筛选方法来分离在大鼠肾小球中主要表达的基因。一些基因已经被分离出来，这些基因在肾小球中主要或唯一表达，尽管它们的序列已经被登记：嗅觉相关蛋白、胸腺素β4、肝素结合的表皮生长因子、VE-钙粘素、βCOP和IV型胶原α3链。一些新的基因也被分离出来，作为肾小球易感基因：14-1和17-3。此外，几个新的基因被鉴定为肾脏特异性或肾脏易感性基因：IG-HEPTA、FR-67和CS-5。其中，对嗅觉相关蛋白和Ig-Hepta的研究较多。嗅球蛋白相关蛋白定位于肾小球足细胞高尔基体及其C端氨基酸序列中，SDEL为高尔基体滞留信号。Ig-Hepta具有2个Ig样结构域和7个跨膜结构域。该分子免疫定位于集合管中的嵌合细胞，提示其在酸碱平衡调节中起作用。

项目成果

Yaoita E, Franke WW, Yamamoto T, Kawasaki K, Kihara I.: "Identification of renal podocytes in multiple species : higher vertebrates are vimentin positive / lower vertebrates are desmin positive."Histochem Cell Biol. 111. 107-115 (1999)

Yaoita E、Franke WW、Yamamoto T、Kawasaki K、Kihara I.：“多个物种肾足细胞的鉴定：高等脊椎动物为波形蛋白阳性/低等脊椎动物为结蛋白阳性。”《组织化学细胞生物学》。

Fujinaka H, Yamamoto T, Takeya M, Feng L, Kawasaki K, Yaoita E, Kondo D, Wilson CB, Uchiyama M, Kihara I.: "Suppression of anti-GBM nephritis by administration of anti-MCP-1 antibody in WKY rats."J Am Soc Nephrol. 8. 1174-1178 (1997)

Fujinaka H、Yamamoto T、Takeya M、Feng L、Kawasaki K、Yaoita E、Kondo D、Wilson CB、Uchiyama M、Kihara I.：“在 WKY 大鼠中施用抗 MCP-1 抗体抑制抗 GBM 肾炎

Goto,Shin: "Involvement of R-cadherin in the early stage of glomerulogenesis." Journal of American Society of Nephrology. 9. 1234-1241 (1998)

Goto,Shin：“R-钙粘蛋白参与肾小球发生的早期阶段。”

Koyama Y 他: "Expression and localization of aquaporins in rat gastrointestinal tract"Am J Physiol. 276. C261-C627 (1999)

Koyama Y 等人：“水通道蛋白在大鼠胃肠道中的表达和定位”Am J Physiol.276.C261-C627(1999)

Funaki H 他: "Immunocalization and Expression of AQP5 in Systemic Organs"Am J Physiol. 275. C1151-C1157 (1998)

Funaki H 等人：“全身器官中 AQP5 的免疫化和表达”Am J Physiol.275.C1151-C1157 (1998)