Phytohormones Affect Differentiation Status of Human Skin Fibroblasts via UPR Activation

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Ekaterina P. Turishcheva^1,a*, Mariya S. Vildanova¹, Polina A. Vishnyakova^2,3, Diana K. Matveeva⁴, Aleena A. Saidova¹, Galina E. Onishchenko¹, and Elena A. Smirnova¹

¹Faculty of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia

²Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Healthcare of the Russian Federation, 117997 Moscow, Russia

³Peoples’ Friendship University of Russia, 117198 Moscow, Russia

⁴Institute of Biomedical Problems, Russian Academy of Sciences, 123007 Moscow, Russia

^* To whom correspondence should be addressed.

Received March 17, 2023; Revised April 28, 2023; Accepted May 2, 2023

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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.

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KEY WORDS: abscisic acid, gibberellic acid, fibroblasts, myofibroblasts, wound healing, fibrosis, differentiation, smooth muscle actin

DOI: 10.1134/S0006297923060093

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