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Transcription Factor KLF2 and Its Role in the Regulation of Inflammatory Processes

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Abstract

KLF2 is a member of the Kruppel-like transcription factor family of proteins containing highly conserved DNA-binding zinc finger domains. KLF2 participates in the differentiation and regulation of the functional activity of monocytes, T lymphocytes, adipocytes, and vascular endothelial cells. The activity of KLF2 is controlled by several regulatory systems, including the MEKK2,3/MEK5/ERK5/MEF2 MAP kinase cascade, Rho family G-proteins, histone acetyltransferases CBP and p300, and histone deacetylases HDAC4 and HDAC5. Activation of KLF2 in endothelial cells induces eNOS expression and provides vasodilatory effect. Many KLF2-dependent genes participate in the suppression of blood coagulation and aggregation of T cells and macrophages with the vascular endothelium, thereby preventing atherosclerosis progression. KLF2 can have a dual effect on the gene transcription. Thus, it induces expression of multiple genes, but suppresses transcription of NF-KB-dependent genes. Transcription factors KLF2 and NF-KB are reciprocal antagonists. KLF2 inhibits induction of NF-KB-dependent genes, whereas NF-KB downregulates KLF2 expression. KLF2-mediated inhibition of NF-KB signaling leads to the suppression of cell response to the pro-inflammatory cytokines IL-ip and TNFa and results in the attenuation of inflammatory processes.

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Abbreviations

AMPK:

AMP-dependent protein kinase

CaMK:

calcium/calmodulin-dependent protein kinase

eNOS:

endothelial nitric oxide synthase

ERK5:

extracellular signal-regulated kinase 5

HDAC:

histone deacetylase

HO-1:

heme oxygenase-1

ICAM-1:

intercellular adhesion molecule-1

KLF:

Kruppel-like factor

MAPK:

mitogen-activated protein kinase

MEF2:

myocyte enhancer factor 2

MEK5:

MAP kinase kinase 5

MEKK:

MAP kinase kinase kinase

PECAM-1:

platelet/endothelial cell adhesion molecule-1

VCAM-1:

vascular cell adhesion molecule-1

VEGF(R):

vascular endothelial growth factor (receptor).

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Authors and Affiliations

  1. Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, 119991, Moscow, Russia

    K. T. Turpaev

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  1. K. T. Turpaev
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Correspondence to K. T. Turpaev.

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Funding

The study was conducted within the frame-work of the State Assignment no. AAAA-A18-118012390247-0.

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The author declares no conflict of interest.

Compliance with ethical standards

Current review contains no description of experiments using human subjects or animals performed by the author.

Russian Text © The Author(s), 2020, published in Biokhimiya, 2020, Vol. 85, No. 1, pp. 64–79.

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Turpaev, K.T. Transcription Factor KLF2 and Its Role in the Regulation of Inflammatory Processes. Biochemistry Moscow 85, 54–67 (2020). https://doi.org/10.1134/S0006297920010058

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  • DOI: https://doi.org/10.1134/S0006297920010058

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