Effect of mechanical stretch on mesangial cells

机械拉伸对系膜细胞的影响

• 批准号: 11671042
• 负责人: KATOH Tetsuo
• 金额: $ 2.24万
• 依托单位: Fukushima Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671042/
• 关键词: TGF-β; Smad; Mesangial cell; collagen; Fibronectine; TGF-β; Collagen; コラーゲン

Mechanical stretch, an in vitro model of glomerular hypertension, increases extracellular matrix (ECM) production via transforming growth factor-β (TGF-β) signaling in cultured rat mesangial cells (MCs). Recently, Smads have been identified as intracellular molecules of TGF-β superfamily. Especially, Smad6 and Smad7 are termed as inhibitory Smads (l-Smads), cause Smad6 and Smad7 have antagonistic a roles through TGF-β signaling. In cultured cells under static condition, exogenous TGF-β 1 up-regulates gene expression of inhibitory Smads gene expression and thereby constituting negative feedback loops in the action of TQF-β. Although various studies of l-Smads were performed under static culture condition, we studied the gene expression of inhibitory Smads in cultured rat mesangial cells under mechanical stretch. Rat MCs were cultured on collagen type I coated plates and stimulated by mechanical stretch or exogenous TGF-β1. Smad6 and Smad7 gene expression were evaluated by northern blot analysis. Relative amount of phospho-Smad2/3 after TGF-β1 treatment was compared with between pre-stretch group and non-stretch group by western blot using anti-phospho-Smad2/3 antibody. In static condition, l-Smads mRNA were significantly increased by exogenous TGF-β1 after 1.5-3 hours and returned to the control levels. Under mechanical stretch (15-20% elongation for 3 hours), although the amount of TGF-β1

机械牵张是一种肾小球高血压的体外模型，通过转化生长因子-β（TGF-β）信号转导增加培养的大鼠系膜细胞（MCs）的细胞外基质（ECM）产生。近年来，Smads被鉴定为TGF-β超家族的细胞内分子。特别是Smad 6和Smad 7被称为抑制性Smads（I-Smads），因为Smad 6和Smad 7通过TGF-β信号通路发挥拮抗作用。在静止培养的细胞中，外源性TGF-β 1上调抑制Smads基因表达的基因表达，从而在TQF-β的作用下形成负反馈环。虽然各种研究的l-Smads进行静态培养条件下，我们研究了抑制性Smads的基因表达在培养的大鼠肾小球系膜细胞在机械拉伸。在I型胶原包被的平板上培养大鼠MCs，并通过机械牵拉或外源性TGF-β1刺激。通过北方印迹分析来评估Smad 6和Smad 7基因表达。用抗磷酸化Smad 2/3抗体进行Western blot，比较TGF-β1处理后、牵张前和非牵张组磷酸化Smad 2/3的相对含量。在静止状态下，外源性TGF-β1刺激1.5 ~ 3 h后，l-Smads mRNA表达显著增加，并恢复到对照组水平。在机械拉伸（15-20%伸长3小时）下，尽管TGF-β1的量

项目成果

M Eiro, T Katoh, Y Sakuma, K Sakurai, H Suzuki, K Asahi, K Watanabe, T Watanabe: "Insulin Resistance Highly Associates with Hypertension in IgA Nephropathy"Clin Nephrol. 59. 71-78 (2003)

M Eiro、T Katoh、Y Sakuma、K Sakurai、H Suzuki、K Asahi、K Watanabe、T Watanabe：“胰岛素抵抗与 IgA 肾病的高血压高度相关”Clin Nephrol。

M Kuriki, K Asahi, K Asano, K Sakurai, M Eiro, H Suzuki, K Watanabe, T Katoh, T Watanabe: "Steroid Therapy Regresses Mesangial Matrix Accumulation in Advanced IgA Nephropathy"Nephrol Dial Transplant. (in press).

M Kuriki、K Asahi、K Asano、K Sakurai、M Eiro、H Suzuki、K Watanabe、T Katoh、T Watanabe：“类固醇疗法可消退晚期 IgA 肾病中的系膜基质积累”肾拨号移植。

H.Watahabe,H.Sanado,S.S.Shigetoni,T.Katoh,T.Watanabe: "Urinary excretion of Type IV Collagen as a specific indicator of the progression of Diabetic Nephropathy."

H.Watahabe、H.Sanado、S.S.Shigetoni、T.Katoh、T.Watanabe：“IV 型胶原蛋白的尿液排泄作为糖尿病肾病进展的特定指标。”

M.Eiro, T.Katoh, Y.Sakuma et al.: "Insulin resistance highly associates with hypertension in IgA nephropathy"Clin.Nephrol.. 59. 71-78 (2003)

M.Eiro、T.Katoh、Y.Sakuma 等：“胰岛素抵抗与 IgA 肾病中的高血压高度相关”Clin.Nephrol.. 59. 71-78 (2003)

K.Kuriki, K.Asahi, K.Asano, K.Sakurai et al.: "Steroid therapy regresses nasalgial matrix accumulation in advanced IgA nephropathy"Nephrol.Dial.Transplant. (in press).

K.Kuriki、K.Asahi、K.Asano、K.Sakurai 等人：“类固醇疗法可消退晚期 IgA 肾病中的鼻腔基质积聚”Nephrol.Dial.Transplant。