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Phytohormones Affect Differentiation Status of Human Skin Fibroblasts via UPR Activation

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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.

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Abbreviations

α-SMA:

α-smooth muscle actin

ABA:

abscisic acid

ATF4:

activating transcription factor 4

CHOP:

CCAAT/enhancer-binding protein homologous protein

ER:

endoplasmic reticulum

GA:

gibberellic acid

GRP78:

glucose-regulated protein 78

PERK:

protein kinase RNA-like endoplasmic reticulum kinase

sXBP1:

spliced X-box binding protein 1

UPR:

unfolded protein response

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Acknowledgments

The authors are grateful to G. A. Ashniev for his assistance in statistical data processing.

Funding

This study was supported by the Russian Foundation for Basic Research (projects nos. 19-015-00233 and 20-315-90118) within the framework of the State Assignment for the Moscow State University no. 121032300098-5.

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Authors and Affiliations

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

    Ekaterina P. Turishcheva, Mariya S. Vildanova, Aleena A. Saidova, Galina E. Onishchenko & Elena A. Smirnova

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

    Polina A. Vishnyakova

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

    Polina A. Vishnyakova

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

    Diana K. Matveeva

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  1. Ekaterina P. Turishcheva
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  2. Mariya S. Vildanova
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  3. Polina A. Vishnyakova
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  4. Diana K. Matveeva
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  5. Aleena A. Saidova
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  6. Galina E. Onishchenko
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  7. Elena A. Smirnova
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Contributions

E.A.S. developed the concept and supervision the study; E.P.T., M.S.V., and D.K.M. performed the experiments; E.P.T., P.A.V., and A.A.S. discussed the results; E.P.T. wrote the article; E.A.S. and G.E.O. edited the manuscript.

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Correspondence to Ekaterina P. Turishcheva.

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The authors declare no conflict of interest. This article does not contain description of studies involving human participants or animals performed by any of the authors.

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Turishcheva, E.P., Vildanova, M.S., Vishnyakova, P.A. et al. Phytohormones Affect Differentiation Status of Human Skin Fibroblasts via UPR Activation. Biochemistry Moscow 88, 810–822 (2023). https://doi.org/10.1134/S0006297923060093

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