抗坏血酸促进转化生长因子β1诱导的肌成纤维细胞表型转换。

Ascorbic acid promotes a TGF1-induced myofibroblast phenotype switch.

作者信息

Piersma Bram, Wouters Olaf Y, de Rond Saskia, Boersema Miriam, Gjaltema Rutger A F, Bank Ruud A

机构信息

Department of Pathology and Medical Biology, Matrix research Group, University of Groningen University Medical Center Groningen, Groningen, The Netherlands

Department of Pathology and Medical Biology, Matrix research Group, University of Groningen University Medical Center Groningen, Groningen, The Netherlands.

出版信息

Physiol Rep. 2017 Sep;5(17). doi: 10.14814/phy2.13324.

l-Ascorbic acid (AA), generally known as vitamin C, is a crucial cofactor for a variety of enzymes, including prolyl-3-hydroxylase (P3H), prolyl-4-hydroxylase (P4H), and lysyl hydroxylase (LH)-mediated collagen maturation. Here, we investigated whether AA has additional functions in the regulation of the myofibroblast phenotype, besides its function in collagen biosynthesis. We found that AA positively influences TGF1-induced expression of , , and Moreover, we demonstrated that AA promotes SMA stress fiber formation as well as the synthesis and deposition of collagens type I and IV Additionally, AA amplified the contractile phenotype of the myofibroblasts, as seen by increased contraction of a 3D collagen lattice. Moreover, AA increased the expression of several TGF1-induced genes, including and Finally, we demonstrated that the mechanism of AA action seems independent of Smad2/3 signaling.

左旋抗坏血酸（AA），通常称为维生素C，是多种酶的关键辅助因子，包括脯氨酰-3-羟化酶（P3H）、脯氨酰-4-羟化酶（P4H）和赖氨酰羟化酶（LH）介导的胶原蛋白成熟过程。在此，我们研究了除了在胶原蛋白生物合成中的作用外，AA在调节肌成纤维细胞表型方面是否还有其他功能。我们发现AA对转化生长因子1（TGF1）诱导的α-平滑肌肌动蛋白（α-SMA）、Ⅰ型胶原蛋白（Col1）和Ⅳ型胶原蛋白（Col4）的表达有正向影响。此外，我们证明AA促进了SMA应力纤维的形成以及Ⅰ型和Ⅳ型胶原蛋白的合成与沉积。另外，如通过三维胶原蛋白晶格收缩增加所显示的，AA增强了肌成纤维细胞的收缩表型。此外，AA增加了几种TGF1诱导基因的表达，包括纤连蛋白（FN）和结缔组织生长因子（CTGF）。最后，我们证明AA的作用机制似乎独立于Smad2/3信号传导。