title: MMP-2 Is Mainly Expressed in Arterioles and Contributes to Cerebral Vascular Remodeling Associated with TGF-β1 Signaling.
abstract: There is increasing evidence to suggest that matrix metalloproteinases (MMPs) play a crucial role in vascular remodeling. It has been reported that hypoxia stimulated MMP-9 expression in brain endothelial cells and MMP-9 plays an important role in cerebral vascular remodeling. However, little is known about MMP-2 in the cerebral vessels remodeling. Herein, the aim of this study is to examine the class of vessel and cell type expressing MMP-2 in cerebral vessels and to investigate its potential role in vascular remodeling. In the present study, dual-immunofluorescence assay showed that MMP-2 was mainly expressed in arterioles. In addition, we found that MMP-2 expression in cerebral vessels was derived from endothelial cells, not astrocyte cells. Notably, in the normoxic central nervous system (CNS), there was no effect on vascular development, integrity, or endothelial proliferation when MMP-2 was knocked out, but lack of MMP-2 led to defective arteriolar remodeling and associated with transforming growth factor β1 (TGF-β1) signaling in CNS. Moreover, blocking TGF-β with SB431542, a specific TGF-β inhibitor, significantly reduced the messenger RNA (mRNA) and protein expression levels of MMP-2 in human umbilical vein endothelial cells (HUVECs). Our findings reveal that the level of MMP-2 is high in arteriolar endothelial cells and demonstrate a novel connection between MMP-2 and TGF-β1 signaling in cerebral vascular remodeling.
authors.affiliation: Department of Neurology, The Affiliated Wuxi Second Hospital, Nanjing Medical University, Zhongshan Road, Wuxi, 214000, Jiangsu, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Hua
authors.affiliation: Department of Neurology, The Affiliated Wuxi Second Hospital, Nanjing Medical University, Zhongshan Road, Wuxi, 214000, Jiangsu, China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The Affiliated Wuxi Second Hospital, Nanjing Medical University, Zhongshan Road, Wuxi, 214000, Jiangsu, China.
authors.forename: Zhenying
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Department of Neurology, The Affiliated Wuxi Second Hospital, Nanjing Medical University, Zhongshan Road, Wuxi, 214000, Jiangsu, China.
authors.forename: Nanfei
authors.initials: N
authors.lastname: Xu
authors.affiliation: Department of Neurology, The Affiliated Wuxi Second Hospital, Nanjing Medical University, Zhongshan Road, Wuxi, 214000, Jiangsu, China. ynlu23@163.com.
authors.forename: Yunnan
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000818:Animals; D001160:Arterioles / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000098:blood supply* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D053773:Transforming Growth Factor beta1; D020778:Matrix Metalloproteinase 2
keywords: Cerebral vessels; Endothelial cell; MMP-2; TGF-β1 signaling; Vascular remodeling