LPS induces HUVEC angiogenesisin vitrothrough miR-146a-mediated TGF-β1 inhibition.
Angiogenesis is an essential process for tissue growth and embryo development. However, inflammation, abnormal wound healing, vascular diseases, and tumor development and progression can result from inappropriate angiogenesis. Lipopolysaccharide (LPS) can activate various cells and alter endothelium function and angiogenesis. This study investigated the underlying molecular events involved in LPS-induced angiogenesis and revealed a novel strategy for controlling abnormal angiogenesis. LPS treatment promoted wound healing and tube formation in human umbilical vein endothelial cell (HUVEC) cultures and induced their expression of miR-146a. miR-146a was previously shown to regulate angiogenesis in HUVECs. Knockdown of miR-146a expression antagonized LPS-induced angiogenesisin vitro. Moreover, bioinformatic analyses predicted TGF-β1 as a target gene for miR-146a, which was confirmed by aluciferase reporter assay. Expression of miR-146a in HUVECs resulted in downregulation of TGF-β1 in HUVECs, whereas a miR-146a inhibitor upregulated the expression of TGF-β1 and TGF-β1 downstream proteins, such as phosphoraylation-Smad2 and plasminogen activator inhibitor type 1 (PAI-1). Furthermore, the TGF-β1 signaling inhibitor SB431542 impaired the ability of miR-146a knockdown to suppress LPS-induced angiogenesis. Thus, LPS-induced angiogenesis of HUVECs functions through miR-146a upregulation and TGF-β1 inhibition. This study suggests that knockdown of miR-146a could activate TGF-β1 signaling to inhibit angiogenesis as a potential therapy for angiogenesis-related diseases.
Department of Clinical Oncology, Xijing Hospital, Fourth Military Medical University Xi'an, Shaanxi, China.
Yize
Y
Li
Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University Xi'an, Shaanxi, China.
Huayu
H
Zhu
The Cadet Brigade, Fourth Military Medical University Xi'an 710032, Shaanxi, China.
Xu
X
Wei
The Cadet Brigade, Fourth Military Medical University Xi'an 710032, Shaanxi, China.
Heng
H
Li
Department of Clinical Oncology, Xijing Hospital, Fourth Military Medical University Xi'an, Shaanxi, China.
Zhicao
Z
Yu
Department of Clinical Oncology, Xijing Hospital, Fourth Military Medical University Xi'an, Shaanxi, China.
Hongmei
H
Zhang
Department of Clinical Oncology, Xijing Hospital, Fourth Military Medical University Xi'an, Shaanxi, China.
Wenchao
W
Liu
Angiogenesis; HUVECs; LPS; TGF-β1; miR-146a