He C J, Striker L J, Tsokos M, Yang C W, Peten E P, Striker G E
Renal Cell Biology Section, National Institute of Diabetes and Digestive and Kidney Disease, National Cancer Institute, Bethesda, Maryland 20892, USA.
Am J Physiol. 1995 Sep;269(3 Pt 1):C554-62. doi: 10.1152/ajpcell.1995.269.3.C554.
Changes in the composition of the mesangial extracellular matrix (ECM) and cell turnover are present in glomerular disease. To determine if ECM changes play a role in perpetuating mesangial cell dysfunction, we examined a line of mouse mesangial cells cultured on films or gels of several ECM components and also on methyl cellulose, an inert substrate that prevents attachment. Cells on films of fibronectin or type IV or I collagen had persistently high growth rates and high levels of alpha 1-I and alpha 1-IV collagen mRNAs. In contrast, on gels of type IV or I collagen or matrigel, the growth rate was low. The alpha 1-IV collagen mRNA levels were low on type IV collagen gel or matrigel, whereas the alpha 1-I collagen mRNA levels remained high. In contrast, the alpha 1-I collagen mRNA levels were low on type I collagen gel, and the alpha 1-IV collagen mRNA levels were high. Cells on methyl cellulose formed floating aggregates, did not proliferate, and had a 5- to 10-fold decrease in both alpha 1-I and alpha 1-IV collagen mRNA levels. These phenotypic changes were largely reversible. Finally, when matrigel was layered over cells on fibronectin films, alpha 1-IV collagen mRNA levels decreased, but alpha 1-I collagen mRNA levels and proliferation remained high. Thus proliferation and alpha 1-I and alpha 1-IV collagen mRNA levels in mesangial cells were independently regulated and depended on attachment and the nature of the adjacent matrix.
肾小球疾病中存在系膜细胞外基质（ECM）组成的变化以及细胞更新。为了确定ECM变化是否在系膜细胞功能障碍的持续存在中起作用，我们检测了在几种ECM成分的薄膜或凝胶上以及在甲基纤维素（一种防止细胞附着的惰性底物）上培养的小鼠系膜细胞系。在纤连蛋白、IV型或I型胶原薄膜上的细胞具有持续较高的生长速率以及较高水平的α1-I和α1-IV胶原mRNA。相比之下，在IV型或I型胶原或基质胶的凝胶上，生长速率较低。在IV型胶原凝胶或基质胶上，α1-IV胶原mRNA水平较低，而α1-I胶原mRNA水平仍然较高。相反，在I型胶原凝胶上，α1-I胶原mRNA水平较低，而α1-IV胶原mRNA水平较高。在甲基纤维素上的细胞形成漂浮聚集体，不增殖，并且α1-I和α1-IV胶原mRNA水平均下降5至10倍。这些表型变化在很大程度上是可逆的。最后，当在纤连蛋白薄膜上的细胞上覆盖基质胶时，α1-IV胶原mRNA水平下降，但α1-I胶原mRNA水平和增殖仍然较高。因此，系膜细胞中的增殖以及α1-I和α1-IV胶原mRNA水平是独立调节的，并且取决于细胞附着以及相邻基质的性质。
