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Article

YAP/TEAD1 Complex Is a Default Repressor of Cardiac Toll-Like Receptor Genes

1
Masonic Medical Research Institute, 2150 Bleecker St, Utica, NY 13501, USA
2
Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, China
3
Department of Neurosurgery, Program on Neurogenetics, Yale School of Medicine, Yale University, New Haven, CT 06510, USA
4
Department of Cardiology, Boston Children’s Hospital, 300 Longwood Ave, Boston, MA 02115, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally.
Academic Editor: Nicole Wagner
Int. J. Mol. Sci. 2021, 22(13), 6649; https://doi.org/10.3390/ijms22136649
Received: 30 May 2021 / Revised: 14 June 2021 / Accepted: 18 June 2021 / Published: 22 June 2021
(This article belongs to the Special Issue Transcriptional Regulation of Cardiac Development and Disease)
Toll-like receptors (TLRs) are a family of pattern recognition receptors (PRRs) that modulate innate immune responses and play essential roles in the pathogenesis of heart diseases. Although important, the molecular mechanisms controlling cardiac TLR genes expression have not been clearly addressed. This study examined the expression pattern of Tlr1, Tlr2, Tlr3, Tlr4, Tlr5, Tlr6, Tlr7, Tlr8, and Tlr9 in normal and disease-stressed mouse hearts. Our results demonstrated that the expression levels of cardiac Tlr3, Tlr7, Tlr8, and Tlr9 increased with age between neonatal and adult developmental stages, whereas the expression of Tlr5 decreased with age. Furthermore, pathological stress increased the expression levels of Tlr2, Tlr4, Tlr5, Tlr7, Tlr8, and Tlr9. Hippo-YAP signaling is essential for heart development and homeostasis maintenance, and YAP/TEAD1 complex is the terminal effector of this pathway. Here we found that TEAD1 directly bound genomic regions adjacent to Tlr1, Tlr2, Tlr3, Tlr4, Tlr5, Tlr6, Tlr7, and Tlr9. In vitro, luciferase reporter data suggest that YAP/TEAD1 repression of Tlr4 depends on a conserved TEAD1 binding motif near Tlr4 transcription start site. In vivo, cardiomyocyte-specific YAP depletion increased the expression of most examined TLR genes, activated the synthesis of pro-inflammatory cytokines, and predisposed the heart to lipopolysaccharide stress. In conclusion, our data indicate that the expression of cardiac TLR genes is associated with age and activated by pathological stress and suggest that YAP/TEAD1 complex is a default repressor of cardiac TLR genes. View Full-Text
Keywords: YAP; TEAD1; Toll-like receptor; heart; TLR4; cardiomyocyte; innate immune responses YAP; TEAD1; Toll-like receptor; heart; TLR4; cardiomyocyte; innate immune responses
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MDPI and ACS Style

Gao, Y.; Sun, Y.; Ercan-Sencicek, A.G.; King, J.S.; Akerberg, B.N.; Ma, Q.; Kontaridis, M.I.; Pu, W.T.; Lin, Z. YAP/TEAD1 Complex Is a Default Repressor of Cardiac Toll-Like Receptor Genes. Int. J. Mol. Sci. 2021, 22, 6649. https://doi.org/10.3390/ijms22136649

AMA Style

Gao Y, Sun Y, Ercan-Sencicek AG, King JS, Akerberg BN, Ma Q, Kontaridis MI, Pu WT, Lin Z. YAP/TEAD1 Complex Is a Default Repressor of Cardiac Toll-Like Receptor Genes. International Journal of Molecular Sciences. 2021; 22(13):6649. https://doi.org/10.3390/ijms22136649

Chicago/Turabian Style

Gao, Yunan, Yan Sun, Adife Gulhan Ercan-Sencicek, Justin S. King, Brynn N. Akerberg, Qing Ma, Maria I. Kontaridis, William T. Pu, and Zhiqiang Lin. 2021. "YAP/TEAD1 Complex Is a Default Repressor of Cardiac Toll-Like Receptor Genes" International Journal of Molecular Sciences 22, no. 13: 6649. https://doi.org/10.3390/ijms22136649

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