Poncelet A C, Schnaper H W
Department of Pediatrics, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Am J Physiol. 1998 Sep;275(3):F458-66. doi: 10.1152/ajprenal.1998.275.3.F458.
Transforming growth factor (TGF)-beta1 has been implicated in glomerular extracellular matrix accumulation. Since the spectrum and mechanism of changes in collagen turnover have not been fully characterized, we evaluated effects of TGF-beta1 on collagen expression by human mesangial cells. TGF-beta1 induced increased alpha1(I), alpha1(III), and alpha1(IV) collagen mRNA expression. Greater mRNA expression of matrix metalloproteinase (MMP)-2 was compensated by increased tissue inhibitor of metalloproteinases (TIMP)-2 mRNA. There was no change in TIMP-1 or membrane-type MMP mRNA expression, whereas MMP-1 mRNA decreased. Types I and IV collagen protein accumulated in both the cell layer and medium. Changes in collagen mRNA and protein occurred within 4 and 8 h, respectively. MMP-2 and TIMP-1 and -2 activities showed little change. Cycloheximide markedly decreased collagen detection within 4 h and reversed late, but not early, changes in alpha1(I) collagen mRNA. In this system, increased synthesis may be more significant than degradation for collagen accumulation, but collagen is short-lived in culture. Diverse TGF-beta1 actions on collagen turnover may be either immediate or mediated through synthesis of regulatory molecules.
转化生长因子（TGF）-β1与肾小球细胞外基质积聚有关。由于胶原周转变化的范围和机制尚未完全明确，我们评估了TGF-β1对人系膜细胞胶原表达的影响。TGF-β1诱导α1（I）、α1（III）和α1（IV）胶原mRNA表达增加。基质金属蛋白酶（MMP）-2的mRNA表达增加被金属蛋白酶组织抑制剂（TIMP）-2 mRNA的增加所补偿。TIMP-1或膜型MMP mRNA表达无变化，而MMP-1 mRNA减少。I型和IV型胶原蛋白在细胞层和培养基中均有积聚。胶原mRNA和蛋白的变化分别在4小时和8小时内出现。MMP-2以及TIMP-1和-2的活性变化不大。放线菌酮在4小时内显著降低了胶原蛋白的检测量，并逆转了α1（I）胶原mRNA的晚期但非早期变化。在该系统中，对于胶原积聚而言，合成增加可能比降解更显著，但胶原在培养中寿命较短。TGF-β1对胶原周转的多种作用可能是即时的，也可能是通过调节分子的合成介导的。
