S100A8/MYD88/NF-қB: a novel pathway involved in cardiomyocyte hypertrophy driven by thyroid hormone.
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-қB), could be associated with the cardiomyocyte hypertrophy induced by TH. Our results demonstrate that the S100A8/MyD88/NF-қB 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-қB activation, which is also involved in the hypertrophic growth of TH-treated cardiomyocytes. Supporting the in vitro data, the contribution of NF-қB for TH-induced cardiac hypertrophy is confirmed in vivo, by using transgenic mice with cardiomyocyte-specific suppression of NF-қB. 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.



Inflammation-related signaling is activated by T3 in cardiomyocytes. S100A8 and MyD88 have a crucial role in cardiomyocyte hypertrophy by T3. S100A8 and MyD88 mediate NF-қB activation by T3. NF-қB contributes to T3-induced cardiac hypertrophy in vitro and in vivo.
Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Ana Paula Cremasco
APC
Takano
Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Carolina Demarchi
CD
Munhoz
Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Anselmo Sigari
AS
Moriscot
Division of Molecular Cardiology, Department of Medical Physiology, College of Medicine, Texas A & M Health Science Center and Scott & White, Central Texas Veterans Health Care System, Temple, TX, USA.
Sudhiranjan
S
Gupta
Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil. mchaves@usp.br.
Maria Luiza Morais
MLM
Barreto-Chaves
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics; D040501:Calgranulin A / Q000235:genetics*; D006332:Cardiomegaly / Q000235:genetics*; D002478:Cells, Cultured; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics*; D020097:Natriuretic Peptide, Brain / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D017208:Rats, Wistar; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics; D014284:Triiodothyronine
D040501:Calgranulin A; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051197:Toll-Like Receptor 4; D014284:Triiodothyronine; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor
Cardiac hypertrophy; Cardiomyocyte; MyD88; NF-қB; S100A8; Thyroid hormone