Conti F G, Striker L J, Elliot S J, Andreani D, Striker G E
Renal Cell Biology Group, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892.
Am J Physiol. 1988 Dec;255(6 Pt 2):F1214-9. doi: 10.1152/ajprenal.1988.255.6.F1214.
Mesangial cell proliferation is a common hallmark of many glomerular diseases. The exact mechanisms inducing cell proliferation in glomerulosclerosis are not completely understood, and it remains to be determined whether growth factors play a role in this process. Insulinlike growth factor I (IGF I) has been shown to be synthesized in the kidney, and glomerular mesangial cells have receptors for and exhibit mitogenic response to IGF I. We found that mouse glomerular mesangial cells in culture synthesized and released into the culture medium a molecule with immunological and biological features of IGF I. This molecule specifically bound to mesangial cell IGF I receptors; high-pressure liquid chromatographic analysis provided further evidence of its similarity to human recombinant IGF I. Mesangial cells released into the culture medium 6 ng/10(6) cells of IGF I-like material per 24 h in a time-dependent and actinomycin-D inhibitable fashion. These data suggest that IGF I might be locally released by mesangial cells in the glomerulus and act in an autocrine and paracrine fashion.
系膜细胞增殖是许多肾小球疾病的共同特征。肾小球硬化中诱导细胞增殖的确切机制尚未完全明了,生长因子是否在此过程中发挥作用仍有待确定。胰岛素样生长因子I(IGF I)已被证明在肾脏中合成,肾小球系膜细胞有IGF I受体并对其表现出促有丝分裂反应。我们发现,培养的小鼠肾小球系膜细胞合成并释放到培养基中的一种分子具有IGF I的免疫学和生物学特性。该分子特异性结合系膜细胞IGF I受体;高压液相色谱分析进一步证明其与人重组IGF I相似。系膜细胞以时间依赖性和放线菌素-D可抑制的方式,每24小时向培养基中释放6 ng/10(6)个细胞的IGF I样物质。这些数据表明,IGF I可能由肾小球中的系膜细胞局部释放,并以自分泌和旁分泌方式发挥作用。