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Suppression of smoo...
Suppression of smooth muscle cell inflammation by myocardin-related transcription factors involves inactivation of TANK-binding kinase 1
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- Bankell, Elisabeth (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Kärlfysiologi,Forskargrupper vid Lunds universitet,Department of Experimental Medical Science,Faculty of Medicine,Vascular Physiology,Lund University Research Groups
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- Liu, Li (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Cellulär biomekanik,Forskargrupper vid Lunds universitet,Kärlfysiologi,Department of Experimental Medical Science,Faculty of Medicine,Cellular Biomechanics,Lund University Research Groups,Vascular Physiology,Guangzhou Medical University
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- van der Horst, Jennifer (author)
- University of Copenhagen
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- Rippe, Catarina (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Cellulär biomekanik,Forskargrupper vid Lunds universitet,Department of Experimental Medical Science,Faculty of Medicine,Cellular Biomechanics,Lund University Research Groups
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- Jepps, Thomas A (author)
- University of Copenhagen
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- Nilsson, Bengt-Olof (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Kärlfysiologi,Forskargrupper vid Lunds universitet,Department of Experimental Medical Science,Faculty of Medicine,Vascular Physiology,Lund University Research Groups
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- Swärd, Karl (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Cellulär biomekanik,Forskargrupper vid Lunds universitet,Department of Experimental Medical Science,Faculty of Medicine,Cellular Biomechanics,Lund University Research Groups
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(creator_code:org_t)
- 2024
- 2024
- English 19 s.
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In: Scientific Reports. - 2045-2322. ; 14:1
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Abstract
Subject headings
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- Myocardin-related transcription factors (MRTFs: myocardin/MYOCD, MRTF-A/MRTFA, and MRTF-B/MRTFB) suppress production of pro-inflammatory cytokines and chemokines in human smooth muscle cells (SMCs) through sequestration of RelA in the NF-κB complex, but additional mechanisms are likely involved. The cGAS-STING pathway is activated by double-stranded DNA in the cytosolic compartment and acts through TANK-binding kinase 1 (TBK1) to spark inflammation. The present study tested if MRTFs suppress inflammation also by targeting cGAS-STING signaling. Interrogation of a transcriptomic dataset where myocardin was overexpressed using a panel of 56 cGAS-STING cytokines showed the panel to be repressed. Moreover, MYOCD, MRTFA, and SRF associated negatively with the panel in human arteries. RT-qPCR in human bronchial SMCs showed that all MRTFs reduced pro-inflammatory cytokines on the panel. MRTFs diminished phosphorylation of TBK1, while STING phosphorylation was marginally affected. The TBK1 inhibitor amlexanox, but not the STING inhibitor H-151, reduced the anti-inflammatory effect of MRTF-A. Co-immunoprecipitation and proximity ligation assays supported binding between MRTF-A and TBK1 in SMCs. MRTFs thus appear to suppress cellular inflammation in part by acting on the kinase TBK1. This may defend SMCs against pro-inflammatory insults in disease.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Keyword
- Humans
- Protein Serine-Threonine Kinases/metabolism
- Nuclear Proteins/metabolism
- Myocytes, Smooth Muscle/metabolism
- Trans-Activators/metabolism
- Inflammation/metabolism
- Signal Transduction
- Cytokines/metabolism
- Phosphorylation
- Transcription Factors/metabolism
- Membrane Proteins/metabolism
- Cells, Cultured
Publication and Content Type
- art (subject category)
- ref (subject category)
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