Cargando…
Thyroid hormone induces artery smooth muscle cell proliferation: discovery of a new TRα1-Nox1 pathway
Thyroid hormone (T3) can stimulate protein synthesis and cell growth. NOX1 is a mitogenic oxidase. The aim of this study was to test a novel hypothesis that T3 induces artery smooth muscle cell proliferation by up-regulating NOX1. Immunofluoresence confocal microscopy was used to visualize the sub-c...
Autores principales: | , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2010
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2888973/ https://www.ncbi.nlm.nih.gov/pubmed/20414976 http://dx.doi.org/10.1111/j.1582-4934.2008.00489.x |
Sumario: | Thyroid hormone (T3) can stimulate protein synthesis and cell growth. NOX1 is a mitogenic oxidase. The aim of this study was to test a novel hypothesis that T3 induces artery smooth muscle cell proliferation by up-regulating NOX1. Immunofluoresence confocal microscopy was used to visualize the sub-cellular localization of NOX1 and TRα1 in rat aorta smooth muscle (RASM) cells. Optical sectioning showed that TRα1 and NOX1 co-localized around the nucleus. T3 promoted RASM cell proliferation as determined by the fact that T3 significantly increased the number of cytokinesis cells, proliferating cellular nuclear antigen (PCNA) and smooth muscle α-actin (SM α-actin). T3 increased NOX1 expression at both the transcription (mRNA) and translation (protein) levels as evaluated by RT-PCR and Western blot, respectively. T3 also significantly increased the intracellular ROS production based on the oxidation of 2’,7’-dichlorodihydrofluoresein (H(2)DCF) to a fluorescent 2’,7’-dichlorofluoresein (DCF). RNAi silence of TRα1 or NOX1 abolished T3-induced intracellular ROS generation and PCNA and SM α-actin expression, indicating that TRα1 and NOX1 mediated T3-induced RASM cell proliferation. Notably, RNAi silence of TRα1 blocked the T3-induced increase in NOX1 expression, whereas silence of NOX1 did not affect TRα1 expression, disclosing a new pathway, i.e. T3-TRα1-NOX1-cell proliferation. TRα1 and NOX1 co-localized around the nucleus. T3 induced RASM cell proliferation by up-regulating NOX1 in a TRα1-dependent manner. |
---|