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Thyroid hormone induces artery smooth muscle cell proliferation: discovery of a new TRα1‐Nox1 pathway
Author(s) -
Wang Xiuqing,
Sun Zhongjie
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1147.11
Subject(s) - nox1 , cell growth , microbiology and biotechnology , actin , proliferating cell nuclear antigen , biology , cell , intracellular , chemistry , biochemistry , reactive oxygen species , nadph oxidase
Hypothesis Thyroid hormone (T3) induces artery smooth muscle cell proliferation by up‐regulating NOX1 dependent on thyroid hormone receptor subtype α1 (TRα1). Methods and Results Immunofluoresence confocal microscopy was used to visualize the sub‐cellular localization of NOX1 and TRα1 in rat aorta smooth muscle (RASM) cells. TRα1 and NOX1 co‐localized in the nuclear periphery. T3 induced RASM cell proliferation as determined by the fact that T3 significantly increased 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. T3 also increased the intracellular ROS production. RNAi silence of TRα1 or NOX1 abolished T3‐induced intracellular ROS generation and PCNA and SM α‐actin expression, indicating that TRα1 and NOX1 mediate 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, suggesting a new pathway, i.e., T3‐TRα1‐NOX1‐cell proliferation. Conclusions TRα1 expressed in RASM cells. TRα1 and NOX1 colocalized in nuclear periphery. T3 induced RASM cell proliferation by up‐regulating NOX1 in a TRα1‐dependent manner.