Wenstrup Richard J, Florer Jane B, Cole William G, Willing Marcia C, Birk David E
Division of Human Genetics, Children's Hospital Research Foundation, Cincinnati, Ohio 45229-3039, USA.
J Cell Biochem. 2004 May 1;92(1):113-24. doi: 10.1002/jcb.20024.
To examine mechanisms by which reduced type V collagen causes weakened connective tissues in the Ehlers-Danlos syndrome (EDS), we examined matrix deposition and collagen fibril morphology in long-term dermal fibroblast cultures. EDS cells with COL5A1 haplo-insufficiency deposited less than one-half of hydroxyproline as collagen compared to control fibroblasts, though total collagen synthesis rates are near-normal because type V collagen represents a small fraction of collagen synthesized. Cells from patients with osteogenesis imperfecta (OI) and haplo-insufficiency for proalpha1(I) chains of type I collagen also incorporated about one-half the collagen as controls, but this amount was proportional to their reduced rates of total collagen synthesis. Collagen fibril diameter was inversely proportional to type V/type I collagen ratios (EDS > control > OI). However, a reduction of type V collagen, in the EDS derived cells, was associated with the assembly of significantly fewer fibrils compared to control and OI cells. These data indicate that in cell culture, the quantity of collagen fibrils deposited in matrix is highly sensitive to reduction in type V collagen, far out of proportion to type V collagen's contribution to collagen mass.
为了研究V型胶原蛋白减少导致埃勒斯-当洛综合征（EDS）中结缔组织减弱的机制，我们检测了长期真皮成纤维细胞培养物中的基质沉积和胶原纤维形态。与对照成纤维细胞相比，COL5A1单倍体不足的EDS细胞沉积的作为胶原蛋白的羟脯氨酸不到对照的一半，尽管由于V型胶原蛋白在合成的胶原蛋白中占比小，总胶原蛋白合成速率接近正常。成骨不全（OI）患者以及I型胶原蛋白原α1（I）链单倍体不足的细胞掺入的胶原蛋白也约为对照的一半，但该量与它们降低的总胶原蛋白合成速率成比例。胶原纤维直径与V型/I型胶原蛋白比率成反比（EDS>对照>OI）。然而，与对照和OI细胞相比，EDS来源的细胞中V型胶原蛋白的减少与显著更少的纤维组装有关。这些数据表明，在细胞培养中，沉积在基质中的胶原纤维数量对V型胶原蛋白的减少高度敏感，与V型胶原蛋白对胶原蛋白总量的贡献远不成比例。
