Effect of glycated collagen on proliferation of human smooth muscle cells in vitro

Effect of glycated collagen on proliferation of human smooth muscle cells in vitro
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DOI:
10.1007/s001250050513
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发表时间:
1996-07
期刊:
影响因子:
8.2
通讯作者:
K. Iino;M. Yoshinari;M. Yamamoto;K. Kaku;Y. Doi;K. Ichikawa;M. Iwase;M. Fujishima
K. Iino;M. Yoshinari;M. Yamamoto;K. Kaku;Y. Doi;K. Ichikawa;M. Iwase;M. Fujishima
中科院分区:
医学1区
文献类型:
--
作者:
K. Iino;M. Yoshinari;M. Yamamoto;K. Kaku;Y. Doi;K. Ichikawa;M. Iwase;M. Fujishima

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虽然长寿组织蛋白(例如胶原蛋白)的非酶糖化与糖尿病的慢性并发症有关,但其在糖尿病大血管病病因学中的作用尚未阐明。为了检验胶原蛋白的糖化消除了天然胶原蛋白对人平滑肌细胞增殖的抑制作用的假设,我们从人胃动脉中获得了平滑肌细胞,并将其培养在涂有糖化或非糖化胶原蛋白的培养皿上。在 10% 胎牛血清或血小板衍生生长因子-BB (10 ng/ml) 存在的情况下,培养皿上涂有 1 型胶原蛋白可抑制人平滑肌细胞的增殖。用葡萄糖 6-磷酸将胶原蛋白糖化 7 天,消除了天然胶原蛋白的生长抑制作用。胶原蛋白的琥珀酰化,就像糖化作用一样,阻断了胶原蛋白中的赖氨酰残基,也消除了生长抑制作用。人平滑肌细胞对胶原蛋白包被的培养皿的粘附不受胶原蛋白糖化的影响。向培养基中添加糖化白蛋白不影响人平滑肌细胞在塑料培养皿上的生长。在氨基胍存在下,胶原蛋白对人平滑肌细胞增殖的抑制不会被胶原蛋白的糖化逆转。结果表明,早期糖化消除了胶原蛋白对人平滑肌细胞增殖的抑制作用,因此可能参与糖尿病大血管病变的进展。
While non-enzymatic glycation of long-lived tissue proteins such as collagen has been implicated in chronic complications of diabetes mellitus, its role in the aetiology of diabetic macroangiopathy has not been elucidated. To test the hypothesis that glycation of collagen abolishes the inhibitory effect of native collagen on the proliferation of human smooth muscle cells, we obtained smooth muscle cells from human gastric arteries and cultured them on dishes coated with glycated or non-glycated collagen. The proliferation of human smooth muscle cells in the presence of 10 % fetal calf serum or platelet derived growth factor-BB (10 ng/ml) was inhibited by type 1 collagen coated on the dishes. Glycation of collagen with glucose 6-phosphate for 7 days abolished the growth-inhibitory effect of native collagen. Succinylation of collagen, which like glycation blocked the lysyl residues in collagen, also abolished the growth-inhibitory effect. Adhesion of human smooth muscle cells to collagen-coated dishes was not affected by glycation of collagen. Addition of glycated albumin to the medium did not affect the growth of human smooth muscle cells on plastic dishes. The inhibition of human smooth muscle cell proliferation by collagen was not reversed by the glycation of collagen in the presence of aminoguanidine. Results suggest that early glycation abolishes the inhibitory effect of collagen on human smooth muscle cell proliferation and may thus participate in the progression of macro-angiopathy in diabetes.