ET-1对系膜细胞增殖和前胶原mRNA表达的影响

Effects of Endothelin-1 on Cultured Rat Glomerular Mesangial Cells Proliferation and Expression ofⅠ,Ⅲ,ⅣType Procollagen mRNA

目的利用已构建的体外肾小球系膜细胞（MC）三维立体培养系统，研究内皮素（ET－1）是否具有刺激MC增殖和表达Ⅰ、Ⅲ、Ⅳ型前胶原mRNA作用。方法3H－TdR掺入法和斑点杂交方法。结果在0．5％小牛血清存在下，10－7mol／LET－1作用12h后，MC对3H－TdR摄入增加（＜0．01），呈剂量依赖方式，＜10－10mol／LET－1对MC无促增殖作用，ET－1≥10-10mol／L时，随着ET－1浓度增加。MC对3H－TdR摄人也增加；在1％小牛血清存在下，10-7mol／LET－1明显促进MC表达Ⅰ、Ⅲ、Ⅳ型前胶原mRNA，而10-12mol／LET－1无此作用。结论ET－1可通过刺激MC增殖和产生细胞外基质促进慢性肾小球疾病病程进展。

Objective To clarify whether endothelin - 1 (ET - 1) can stimulate mesangialcell(MC) mitogenesis and expression of Ⅰ. Ⅲ. Ⅳ type procollagen mRNA in three dimensional extracellular matrix MC culture system. Methods In our study, 3H - TdR incorporation and dot hybridization methods were used. Results In the presence of 0.5% bovine serum and after incubation for 12h with 10-7 mol/L ET- 1, 3H - TdR incorporation in MCs was significantly increased (P<0.01), the reaction was dose dependent, doses of ET- 1 less than 10-10 mol/L had no influence on 3H - TdR incorporation, while those ≥10-10 mol/L had noeffect on 3H - TdR incorporation, and the greater the dosage of ET - 1, the higher 3H - TdR incorporation. In the presence of 1% bovine serum, 10-7 mol/L ET- 1 markedly increased MCs expression of Ⅰ. Ⅲ. Ⅳ type procollagen mRNA, but 10-12 mol/L ET - 1 had no effect on the expression of Ⅰ. Ⅲ. Ⅳ type procollagen mRNA. Conclusion ET - 1 may accelerate the progression of chronic glomerular diseases by stimulating MCs proliferation and production of extracellular matrix.