Article

Molecular and Cellular Biochemistry

, Volume 375, Issue 1, pp 11-21

First online:

Transforming growth factor-β1 induces matrix metalloproteinase-9 expression in rat vascular smooth muscle cells via ROS-dependent ERK–NF-κB pathways

  • Hao ZhangAffiliated withDepartment of Cardiothoracic Surgery, Renmin Hospital of Wuhan UniversityDepartment of Cardiothoracic Surgery, Xiangyang Central Hospital
  • , Zhi-Wei WangAffiliated withDepartment of Cardiothoracic Surgery, Renmin Hospital of Wuhan University Email author 
  • , Hong-Bing WuAffiliated withDepartment of Cardiothoracic Surgery, Renmin Hospital of Wuhan University
  • , Zhi LiAffiliated withDepartment of Ophtalmology, Xiangyang Central Hospital
  • , Luo-Cheng LiAffiliated withDepartment of Cardiothoracic Surgery, Renmin Hospital of Wuhan University
  • , Xiao-Ping HuAffiliated withDepartment of Cardiothoracic Surgery, Renmin Hospital of Wuhan University
  • , Zong-Li RenAffiliated withDepartment of Cardiothoracic Surgery, Renmin Hospital of Wuhan University
  • , Bai-Jun LiAffiliated withDepartment of Cardiothoracic Surgery, Renmin Hospital of Wuhan University
  • , Zhi-Peng HuAffiliated withDepartment of Cardiothoracic Surgery, Renmin Hospital of Wuhan University

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract

Both matrix metalloproteinase-9 (MMP9) and transforming growth factors-β1 (TGF-β1) are the important factors in the pathogenesis of the aortic aneurysm (AA) and aortic dissection (AD). Recent studies have shown that inhibition of reactive oxygen species (ROS) production, extracellular signal–regulated kinase 1/2(ERK1/2) or NF-κB pathways is able to suppress aneurysm formation. The median layers of arterial walls are mainly the vascular smooth muscle cells (VSMCs), while the pathogenesis of AA and AD is closely related to the changes in the median layer structure. Thus, we investigated the molecular mechanisms underlying TGF-β1-induced MMP-9 expression in VSMC, the involvement of intracellular ROS and signaling molecules, including ERK1/2 and NF-κB. Rat vascular smooth muscle cells (A7r5) were used. MMP-9 expression was analyzed by gelatin zymography, western blot and RT-PCR. The involvement of intracellular ROS and signaling molecules including ERK1/2 and NF-κB in the responses was investigated using reactive oxygen scavenger N-acetylcysteine (NAC) and pharmacological inhibitors (U0126 and BAY11-7082), determined by ROS testing and western blot testing for their corresponding proteins. TGF-β1 induces MMP-9 expression via ROS-dependent signaling pathway. ROS production leads to activation of ERK1/2 and then activation of the NF-κB transcription factor. Activated NF-κB turns on transcription of the MMP-9 gene. The process in which TGF-β1 induces MMP9 expression involves the ROS-dependent ERK–NF-κB signal pathways in VSMC. This discovery raises a new regulation pathway in the VSMC, and it shows the potential to help to find a new solution to treating aortic aneurysm and aortic dissection.

Keywords

TGF-β1 MMP9 VSMC ROS ERK NF-κB