S100A8/MYD88/NF-O > B: a novel pathway involved in cardiomyocyte hypertrophy driven by thyroid hormone

Author(s)

Cremasco Takano, Ana Paula ; Munhoz, Carolina Demarchi ; Moriscot, Anselmo Sigari ; Gupta, Sudhiranjan ; Morais Barreto-Chaves, Maria Luiza

• Document type: Journal article
• Source: JOURNAL OF MOLECULAR MEDICINE-JMM; v. 95, n. 6, p. 671-682, JUN 2017.
• Web of Science Citations: 4

Abstract

Recent studies have evidenced the involvement of inflammation-related pathways to the development of cardiac hypertrophy and other consequences on the cardiovascular system, including the calcium-binding protein S100A8. However, this has never been investigated in the thyroid hormone (TH)-prompted cardiac hypertrophy. Thus, we aimed to test whether S100A8 and related signaling molecules, myeloid differentiation factor-88 (MyD88) and nuclear factor kappa B (NF-kappa B), could be associated with the cardiomyocyte hypertrophy induced by TH. Our results demonstrate that the S100A8/MyD88/NF-kappa B signaling pathway is activated in cardiomyocytes following TH stimulation. The knockdown of S100A8 and MyD88 indicates the contribution of those molecules to cardiomyocyte hypertrophy in response to TH, as evaluated by cell surface area, leucine incorporation assay, and gene expression. Furthermore, S100A8 and MyD88 are crucial mediators of NF-kappa B activation, which is also involved in the hypertrophic growth of TH-treated cardiomyocytes. Supporting the in vitro data, the contribution of NF-kappa B for TH-induced cardiac hypertrophy is confirmed in vivo, by using transgenic mice with cardiomyocyte-specific suppression of NF-kappa B. These data identify a novel pathway regulated by TH that mediates cardiomyocyte hypertrophy. However, the potential role of this new pathway in short and long-term cardiac effects of TH remains to be further investigated. (AU)

• FAPESP's process: 11/23352-4 - Association between inflammation-related pathways and cardiac hypertrophy induced by thyroid hormone. Role of the Renin-Angiotensin System
• Grantee: Ana Paula Cremasco Takano
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 15/01166-5 - Effect of cardiac specific inhibition of NF-kB in cardiac hypertrophy induced by thyroid hormone
• Grantee: Ana Paula Cremasco Takano
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 13/22480-4 - Inflammation and cardiac hypertrophy induced by thyroid hormones: contribution of renin-angiotensin system
• Grantee: Maria Luiza de Morais Barreto de Chaves
• Support Opportunities: Regular Research Grants