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转化生长因子β1影响人成骨样细胞中I型胶原蛋白的赖氨酰羟化作用,并降低赖氨酰羟化酶mRNA的稳态水平。

Transforming growth factor beta 1 influences lysyl hydroxylation of collagen I and reduces steady-state levels of lysyl hydroxylase mRNA in human osteoblast-like cells.

作者信息

Seitzer U, Bätge B, Acil Y, Müller P K

机构信息

Institut für Medizinische Molekularbiologie, Medizinische Universität zu Lübeck, Germany.

出版信息

Eur J Clin Invest. 1995 Dec;25(12):959-66. doi: 10.1111/j.1365-2362.1995.tb01974.x.

DOI:10.1111/j.1365-2362.1995.tb01974.x
PMID:8719938
Abstract

Transforming growth factor beta 1 (TGF-beta 1) is an osteotropic growth factor that is found in substantial concentration in bone. The authors studied the influence of TGF-beta 1 on the modification of lysine residues of collagen I. The degree of lysyl hydroxylation and lysyl glycosylation of newly synthesized collagen as well as steady-state levels of mRNA for both lysyl hydroxylase and collagens I and III were determined in human osteoblast-like cells in vitro. In normal human osteoblasts lysyl hydroxylation was decreased by TGF-beta 1 particularly in the collagen alpha 2-chain. This effect was paralleled by an increase in lysyl residues, whereas glycosylation was not affected. The mRNA for lysyl hydroxylase was reduced by one-third under the influence of TGF-beta 1. Additionally, the mRNAs for both procollagen I alpha-chains were stimulated by TGF-beta 1, whereas pro alpha 1 (III)-mRNA showed a decrease. Changes in the local regulatory activity of TGF-beta 1 may play a role in matrix maturation such as collagen type production and lysyl hydroxylation, the latter being altered in various pathological conditions, e.g. in generalized osteopenia.

摘要

转化生长因子β1(TGF-β1)是一种促骨生长因子,在骨组织中含量丰富。作者研究了TGF-β1对I型胶原赖氨酸残基修饰的影响。在体外培养的人成骨样细胞中,测定了新合成胶原的赖氨酰羟化程度和赖氨酰糖基化程度,以及赖氨酰羟化酶、I型胶原和III型胶原mRNA的稳态水平。在正常人成骨细胞中,TGF-β1可降低赖氨酰羟化,尤其是在胶原α2链中。这种作用伴随着赖氨酸残基的增加,而糖基化不受影响。在TGF-β1的影响下,赖氨酰羟化酶的mRNA减少了三分之一。此外,TGF-β1可刺激I型前胶原α链的mRNA,而α1(III)-前胶原mRNA则减少。TGF-β1局部调节活性的变化可能在基质成熟过程中发挥作用,如胶原类型的产生和赖氨酰羟化,后者在各种病理状态下会发生改变,如在全身性骨质减少中。

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