Abstract：
Normalization of secretory activity and differentiation status of mesenchymal cells, including fibroblasts, is an important biomedical problem. One of the possible solutions is modulation of unfolded protein response (UPR) activated during fibroblast differentiation. Here, we investigated the effect of phytohormones on the secretory activity and differentiation of cultured human skin fibroblasts. Based on the analysis of expression of genes encoding UPR markers, abscisic acid (ABA) upregulated expression of the GRP78 and ATF4 genes, while gibberellic acid (GA) upregulated expression of CHOP. Evaluation of the biosynthetic activity of fibroblasts showed that ABA promoted secretion and synthesis of procollagen I and synthesis of fibronectin, as well as the total production of collagen and non-collagen proteins of the extracellular matrix (ECM). ABA also stimulated the synthesis of smooth muscle actin α (α-SMA), which is the marker of myofibroblasts, and increased the number of myofibroblasts in the cell population. On the contrary, GA increased the level of fibronectin secretion, but reduced procollagen I synthesis and the total production of the ECM collagen proteins. GA downregulated the synthesis of α-SMA and decreased the number of myofibroblasts in the cell population. Our results suggest that phytohormones modulate the biosynthetic activity of fibroblasts and affect their differentiation status.
摘要：
间充质细胞分泌活性和分化状态的正常化,包括成纤维细胞,是一个重要的生物医学问题。可能的解决方案之一是在成纤维细胞分化过程中激活的未折叠蛋白质反应（UPR）的调节。这里,我们研究了植物激素对培养的人皮肤成纤维细胞分泌活性和分化的影响。基于编码UPR标记的基因的表达分析，脱落酸（ABA）上调GRP78和ATF4基因的表达，赤霉素(GA)上调CHOP的表达。对成纤维细胞生物合成活性的评价显示ABA促进I型前胶原的分泌和合成以及纤连蛋白的合成,以及细胞外基质（ECM）的胶原蛋白和非胶原蛋白的总产量。ABA还刺激平滑肌肌动蛋白α（α-SMA）的合成，这是肌成纤维细胞的标志，并增加细胞群中肌成纤维细胞的数量。相反,GA增加了纤维连接蛋白的分泌水平，但降低了前胶原I的合成和ECM胶原蛋白的总产量。GA下调α-SMA的合成并减少细胞群中肌成纤维细胞的数量。我们的结果表明，植物激素调节成纤维细胞的生物合成活性并影响其分化状态。
