Phytohormones affect the differentiation of human dermal fibroblasts via UPR activation

Abstract

Normalization of secretory activity and the level of differentiation of mesenchymal cells, including fibroblasts, is the important biomedical problem. One of the plausible solutions to this problem is to affect the unfolded protein response (UPR) signaling cascade, which is activated during fibroblast differentiation. In the present study, the effect of phytohormones on the secretory activity and differentiation of cultured human dermal fibroblasts was investigated. By analyzing the expression level of genes encoding UPR markers in these cells, we found that phytohormone abscisic acid (ABA) upregulated the expression of GRP78 and ATF4 genes, while phytohormone gibberellic acid (GA) upregulated the expression of CHOP. Evaluation of the biosynthetic activity of fibroblasts showed that ABA elevated the level of secretion and synthesis of procollagen I and the level of fibronectin synthesis, as well as total production of collagen and non-collagen proteins of extracellular matrix. ABA also stimulated the synthesis of smooth muscle actin α (α-SMA) and increased the number of myofibroblasts in cell population. On the contrary, GA increased the level of fibronectin secretion, but decreased the level of procollagen I synthesis, and reduced the total production of collagen proteins of extracellular matrix. Concomitantly, in these conditions we observed the decreased level of α-SMA synthesis and the number of myofibroblasts in the cell population. Our results suggest that phytohormones are the modulators of the biosynthetic activity of fibroblasts and affect their differentiation status.