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Inhibition of Integrin-Associated Kinases FAK and ILK on the In Vitro Model of Skin Wound Healing

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Abstract

Dermal fibroblasts are essential cells of skin tissue responsible for its normal functioning. In skin wounds, the differentiation of resident fibroblasts into myofibroblasts occurs, which is accompanied by the rearrangement of actin cytoskeleton with the expression of alpha-smooth muscle actin. This transformation is a prerequisite for a successful wound healing. At the same time, different studies indicate that extracellular matrix may be involved in regulation of this process. Since the connection between cells and matrix is provided by transmembrane integrin receptors, this work was aimed at studying the dynamics of signaling pathways associated with integrins on an in vitro model of wound healing using human skin fibroblasts. It was shown that the healing of simulated wound was accompanied by a change in the level of integrins as well as integrin-associated kinases ILK (integrin-linked kinase) and FAK (focal adhesion kinase). Pharmacological inhibition of ILK and FAK caused the suppression of p38 and Akt which proteins are involved in regulation of the actin cytoskeleton. Moreover, it resulted in an inefficient wound closure in vitro. The results of this study support the involvement of integrin-associated kinases in regulation of fibroblast-to-myofibroblast transition during wound healing.

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Fig. 1
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Data availability

Data generated or analyzed during this study are included in this article.

Abbreviations

αSMA:

Alpha-smooth muscle actin

TGFβ1:

Transforming growth factor-beta1

ВКМ:

Extracellular matrix

ILK:

Integrin-linked kinase

FAK:

Focal adhesion kinase

Intβ1:

Integrin beta1

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Funding

This work was supported by the Ministry of Science and Higher Education of the Russian Federation (agreement no. 075-15-2020-773 and theme no. FMFU-2021-0008) and the Institute of Cytology (INC RAS) Director’s Fund.

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  1. Institute of Cytology Russian Academy of Sciences, Centre for Cell Technologies, Tikhoretsky ave. 4, 194064, Saint Petersburg, Russia

    Natalya Bildyug

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  1. Natalya Bildyug
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Study conception and design, experimentations, data collection and analysis, and manuscript preparation: Natalya Bildyug.

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Correspondence to Natalya Bildyug.

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Bildyug, N. Inhibition of Integrin-Associated Kinases FAK and ILK on the In Vitro Model of Skin Wound Healing. Appl Biochem Biotechnol (2024). https://doi.org/10.1007/s12010-023-04842-x

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