ROLE OF AND REGULATION OF GROWTH FACTOR TGF-β IN GLOMERULAR LESIONS

生长因子TGF-β在肾小球病变中的作用和调节

• 批准号: 15590869
• 负责人: OKUDA Seiya
• 金额: $ 2.18万
• 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: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590869/
• 关键词: Growth factor; TGF-β; Soluble receptor; Glomerulosclerosis; Renal fibrosis; matrix; TGF-β acctivation; LTBP

The extracellular domain of TGF-β type 2 receptor can bind active TGF-β tightly but does not involve signal transduction of TGF-β. Therefore, a large amount of TGF-β soluble receptor can prevent TGF-β binding to true TGF-β receptor. To investigate the effects of TGF-β soluble receptor on TGF-β action in vivo, the gene of TGF-β type 2 receptor extracellular domain was transfected into the muscle of rats by using 5x10^8 recombinant adenovirus vector at 1 days before the unilateral uretal obstruction. Serum concentration of TGF-β soluble receptor was quantitated by ELISA assay. The serum concentration of the soluble receptor at 10 days after the transfection was 70ng/ml, which was 50-fold higher than reported concentration of active form TGF-β in rats serum and considered to be sufficient to block the active TGF-β in vivo. Tubular damage and interstitial fibrosis were marked in ureteral obstruction rat kidney. These lesions were attenuated by the elevated level of the TGF-β soluble receptor. Interstitial fibronectin accumulation, vimentin expression and macrophage accumulation were markedly decreased by the TGF-β soluble receptor gene tranfection. TGF-β type 2 soluble receptor is a potent inhibitor of TGF-β to modulate renal fibrosis.

TGF-β 2型受体胞外结构域能与活性TGF-β紧密结合，但不参与TGF-β的信号转导。因此，大量的TGF-β可溶性受体可以阻止TGF-β与真正的TGF-β受体结合。为了研究TGF-β可溶性受体在体内对TGF-β作用的影响，在单侧输尿管梗阻前1天，用5 × 10^8重组腺病毒载体将TGF-β 2型受体胞外结构域基因转染大鼠肌肉。ELISA法测定血清TGF-β可溶性受体浓度。转染后10天血清可溶性受体浓度为70ng/ml，比已有报道的大鼠血清活性形态TGF-β浓度高50倍，认为足以阻断体内活性TGF-β。输尿管梗阻大鼠肾小管损伤及间质纤维化明显。TGF-β可溶性受体水平升高可减轻这些病变。TGF-β可溶性受体基因转染后，间质纤维连接蛋白积累、波形蛋白表达和巨噬细胞积累均明显减少。TGF-β 2型可溶性受体是TGF-β调控肾纤维化的有效抑制剂。

项目成果

Role of TGF-b in the progression of renal flbrosis.

TGF-b 在肾纤维化进展中的作用。

• 发表时间: 2003
• 期刊: Contrin Nephrol 139
• 作者: Tamaki K;Okuda S
• 通讯作者: Okuda S

Risk factors for renal glomerular and vascular changes in an autpsy-based population survey : The Hisayama study.

基于尸检的人群调查中肾小球和血管变化的危险因素：久山研究。

• 发表时间: 2003
• 期刊: Kidney Int 63
• 作者: Nangaku M;Miyata T;Sada T;Mizuno M;Inagi R;Ueda Y;Ishikawa N;Yuzawa H;Koike H;Van Ypersele De Strihou C;Kurokawa K.;Okuda.S
• 通讯作者: Okuda.S

Smad protein and TGF-b signaling in vascular smooth muscle cells.

血管平滑肌细胞中的 Smad 蛋白和 TGF-b 信号传导。

• 发表时间: 2003
• 期刊: Int J Mol Med 11
• 作者: Ikedo H;Tamaki K;Ueda S;Kato S;Hujii M;TenDuke P;Okuda S
• 通讯作者: Okuda S

Okuda S: "Role of TGF-b in the progression of renal fibrosis."Contrin Nephrol. 139. 44-65 (2003)

Okuda S：“TGF-b 在肾纤维化进展中的作用。”Contrin Nephrol。

Okuda S: "Risk factors for renal glomerular and vascular changes in an autpsy-based population survey. The Hisayama study."Kidney Int. 63. 1508-1515 (2003)

Okuda S：“基于自检的人群调查中肾小球和血管变化的危险因素。久山研究。”Kidney Int。