Schreiber B D, Hughes M L, Groggel G C
Department of Medicine, University of Vermont College of Medicine, Burlington, USA.
Clin Nephrol. 1995 Jun;43(6):368-74.
Diabetic nephropathy is characterized by mesangial cell proliferation and expansion of the mesangial matrix. Insulin-like growth factor-1 (IGF-1) increases in the kidney early in experimental diabetes. The effect of IGF-1 on mesangial cell proliferation and synthesis of extracellular matrix (ECM) proteins was examined to test the hypothesis that IGF-1 stimulates mesangial cells to synthesize ECM proteins. ECM proteins were measured by immunoprecipitation after metabolic labeling of rat mesangial cells in culture. IGF-1 caused a 2.4-fold increase in mesangial cell proliferation as measured by 3H-thymidine incorporation. IGF-1 caused an increase in cellular laminin, fibronectin and type IV collagen, 46.8 +/- 15.4%, 31.3 +/- 11.4%, and 27.7 +/- 12.6% increase respectively compared to control cells. IGF-1 did not effect cellular type 1 collagen, decrease of 8.2 +/- 8.7%. There was a trend toward increased total protein synthesis by IGF-1, 36.5 +/- 2.5%. In summary, IGF-1 stimulates ECM component production by mesangial cells. Thus, IGF-1 has the capacity to mediate the histologic changes characteristic of diabetic nephropathy.
糖尿病肾病的特征是系膜细胞增殖和系膜基质扩张。在实验性糖尿病早期，肾脏中的胰岛素样生长因子-1（IGF-1）会增加。研究了IGF-1对系膜细胞增殖和细胞外基质（ECM）蛋白合成的影响，以检验IGF-1刺激系膜细胞合成ECM蛋白这一假说。在对培养的大鼠系膜细胞进行代谢标记后，通过免疫沉淀法测定ECM蛋白。通过3H-胸腺嘧啶核苷掺入法测定，IGF-1使系膜细胞增殖增加了2.4倍。与对照细胞相比，IGF-1使细胞层粘连蛋白、纤连蛋白和IV型胶原分别增加了46.8±15.4%、31.3±11.4%和27.7±12.6%。IGF-1对细胞I型胶原没有影响，下降了8.2±8.7%。IGF-1使总蛋白合成有增加的趋势，为36.5±2.5%。总之，IGF-1刺激系膜细胞产生ECM成分。因此，IGF-1有能力介导糖尿病肾病的组织学特征性变化。
