REGULATION OF TGF-beta ACTIVITY FOR ATTENUATION OF GLOMERULAR LESIONS

调节 TGF-β 活性以减轻肾小球病变

• 批准号: 08671289
• 负责人: OKUDA Seiya
• 金额: $ 1.34万
• 依托单位: KURUME UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671289/
• 关键词: Growth factor; TGF-beta; Soluble receptor; Glomerulosclerosis; Renal fibrosis; matrix; TGF-beta localization; TGF-beta acctivation; 糸球体疾患; マトリックス; TGF-βレセプター; LTBP; アデノウイルス; 遺伝子導入

1.The latency of TGF-beta and chronicity of renal diseasesOur previous studies demonstrated that in a chronic renal disease model, most of TGF-beta is not activated and exsits as a latent form in tissue. The tissue storage of latent TGF-beta may be important for chronicity of histological changes. Tissue localization of latent TGF-beta was examined in vitro and in vivo. The matrices from mesangial cell cultures were shown to contain a large amount of latent TGF-beta. In an experimental FGS model, latent TGF-beta accumulates in the sclerosing glomeruli and the fibrous interstitium extensively and coexists with the other matrix proteins. The matrix-associated latent TGF-beta may serve as a chronic stimulus driving new ECM synthesis, which is important for both keeping and developing sclerosis or fibrotic tissues.2.The effect of TGF-beta soluble receptor on renal fibrosisThe TGF-beta soluble receptor, which is extracellular domain of TGF-beta type 2 receptor has been expected to inhibit TGF-beta action in renal diseases. The gene of the soluble receptor was transfectd to muscle in rats with unilateral ureter obstruction, using adenovirus vectors. The interstitial fibrosis was attenuated in association with the increased serum levels of the soluble receptor. TGF-beta soluble receptor is a potent inhibitor of TGF-beta to modulate renal histological lesions.

1.TGF-β的潜伏期与肾脏疾病的慢性化我们前期的研究表明，在慢性肾脏病模型中，大部分TGF-β不被激活，以潜伏形式存在于组织中。潜在 TGF-β 的组织储存对于组织学变化的长期性可能很重要。在体外和体内检查了潜在 TGF-β 的组织定位。系膜细胞培养物的基质显示含有大量潜在的 TGF-β。在实验性 FGS 模型中，潜在的 TGF-β 在硬化性肾小球和纤维间质中广泛积累，并与其他基质蛋白共存。基质相关的潜在TGF-β可能作为驱动新ECM合成的慢性刺激物，这对于硬化或纤维化组织的维持和发展都很重要。2.TGF-β可溶性受体对肾纤维化的作用TGF-β可溶性受体是TGF-β2型受体的胞外结构域，预计可以抑制TGF-β的作用 在肾脏疾病中。使用腺病毒载体将可溶性受体的基因转染到单侧输尿管梗阻大鼠的肌​​肉中。间质纤维化的减弱与可溶性受体血清水平的增加有关。 TGF-β 可溶性受体是 TGF-β 的有效抑制剂，可调节肾脏组织学病变。

项目成果

Kubo M,Hirakata H,Okuda S et al: "Angiotensin I converting enzume inhibitor and worsening of anemia in hemodialysis patients : Prevention with rHuEPO." J Jpn Dial Ther. 30. 315-320 (1997)

Kubo M、Hirakata H、Okuda S 等人：“血管紧张素 I 转换酶抑制剂和血液透析患者贫血恶化：用 rHuEPO 预防。”

Okuda S: "Role of endothelin as a mitogen in experimental glomerulonephritis in rats." Kidney Int. 49. 1320-1329 (1996)

Okuda S：“内皮素作为有丝分裂原在大鼠实验性肾小球肾炎中的作用。”

Fukuda K: "Role of endothelin as a mitogen in experimental glomerulonephritis in rats." Kidney International. 49. 1320-1329 (1996)

Fukuda K：“内皮素作为有丝分裂原在大鼠实验性肾小球肾炎中的作用。”

Nakayama M: "Short-or long term effects of a low-protein diet on fibronectin and transforming growth factor-β synthesis in adriamycin-induced nephropathy." Journal of Labratory of Clinical Medicine. 127. 29-39 (1996)

Nakayama M：“低蛋白饮食对阿霉素诱发肾病中纤连蛋白和转化生长因子-β 合成的短期或长期影响。临床医学实验室杂志 127. 29-39 (1996)”

Okuda S: "Short-or long term effects of a low-protein diet on fibronectin and ransforming growth factor-b synthesis in adriamycin-induced nephropathy." J Lab Clin Med. 127. 29-39 (1996)

Okuda S：“低蛋白饮食对阿霉素诱发肾病中纤连蛋白和转化生长因子 B 合成的短期或长期影响。”