Kindlin-2 mediates mechanical activation of cardiac myofibroblasts
Abstract: We identify the focal adhesion protein kindlin-2 as player in a novel mechanotransduction pathway that controls profibrotic cardiac fibroblast to myofibroblast activation. Kindlin-2 is co-upregulated with the myofibroblast marker α-smooth muscle actin (α-SMA) in fibrotic rat hearts and in human cardiac fibroblasts exposed to fibrosis-stiff culture substrates and pro-fibrotic TGF-β1. Stressing fibroblasts using ferromagnetic microbeads, stretchable silicone membranes, and cell contraction agonists all result in kindlin-2 translocation to the nucleus. Overexpression of full-length kindlin-2 but not of kindlin-2 missing a putative nuclear localization sequence (∆NLS kindlin-2) results in increased α-SMA promoter activity. Downregulating kindlin-2 with siRNA leads to decreased myofibroblast contraction and reduced α-SMA expression, which is dependent on CC(A/T)-rich GG(CArG) box elements in the α-SMA promoter. Lost myofibroblast features under kindlin-2 knockdown are rescued with wild-type but not ∆NLS kindlin-2, indicating that myofibroblast control by kindlin-2 requires its nuclear translocation. Because kindlin-2 can act as a mechanotransducer regulating the transcription of α-SMA, it is a potential target to interfere with myofibroblast activation in tissue fibrosis
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Notes
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Cells. - 9, 12 (2020) , 2702, ISSN: 2073-4409
- Event
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Veröffentlichung
- (where)
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Freiburg
- (who)
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Universität
- (when)
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2021
- Creator
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Godbout, Elena
Son, Dong Ok
Hume, Stephanie
Boo, Stellar
Sarrazy, Vincent
Clément, Sophie
Kapus, Andras
Wehrle-Haller, Bernhard
Bruckner-Tuderman, Leena
Has, Cristina
Hinz, Boris
- DOI
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10.3390/cells9122702
- URN
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urn:nbn:de:bsz:25-freidok-1749299
- Rights
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Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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25.03.2025, 1:51 PM CET
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Godbout, Elena
- Son, Dong Ok
- Hume, Stephanie
- Boo, Stellar
- Sarrazy, Vincent
- Clément, Sophie
- Kapus, Andras
- Wehrle-Haller, Bernhard
- Bruckner-Tuderman, Leena
- Has, Cristina
- Hinz, Boris
- Universität
Time of origin
- 2021
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