Details

Autor(en) / Beteiligte

• Liu, Xin-Hua
• Zhang, Qiu-Yan
• Pan, Li-Long
• Liu, Si-Yu
• Xu, Peng
• Luo, Xiao-Ling
• Zou, Si-Li
• Xin, Hong
• Qu, Le-Feng
• Zhu, Yi-Zhun

Titel

NADPH oxidase 4 contributes to connective tissue growth factor expression through Smad3-dependent signaling pathway

Ist Teil von

• Free radical biology & medicine, 2016-05, Vol.94, p.174-184

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• Transforming growth factor-β (TGF-β)/Smad signaling has been implicated in connective tissue growth factor (CTGF) expression in vascular smooth muscle cells (VSMC). Reactive oxygen species (ROS) are involved in activation of TGF-β/Smad signaling. However, detailed mechanisms underlying the process remain unclear. In present study, we demonstrated TGF-β1 strongly induced CTGF expression, Smad3 activation, NADPH oxidase 4 (Nox4) expression and increased ROS production in primary rat VSMC in vitro. NADPH oxidases inhibitor diphenylene iodonium (DPI) eliminated TGF-β1-induced CTGF expression and ROS generation. In addition, small-interfering RNA (siRNA) silencing of Smad3 or Nox4 significantly suppressed TGF-β1-mediated CTGF expression in VSMC. Furthermore, Nox4 silencing or inhibition eliminated TGF-β1-induced Smad3 activation and interaction between Nox4 and Smad3. In vivo studies further identified a positive correlation of Nox4 levels with Smad3 activation and CTGF expression in atherosclerotic arteries of patients and animal models. These data established that a novel mechanistic link of Nox4-dependent activation of Smad3 to increased TGF-β1-induced CTGF in the process of vascular remodeling, which suggested a new potential pathway for therapeutic interventions. •Upregulation of Nox4 and CTGF expression in the atherosclerosis.•Smad3-dependent pathway mediates TGF-β1-induced CTGF expression.•Nox4 and Smad3 are responsible for TGF-β1-evoked CTGF expression.•Nox4 modulates TGF-β1-mediated Smad3 signaling activation.