Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8321888 | The International Journal of Biochemistry & Cell Biology | 2018 | 29 Pages |
Abstract
Lymphangiogenesis has been regarded as a physiological response to pathologic stimuli. The abnormal proliferation of lymphatic endothelial cell (LECs) and lymphangiogenesis is involved in the development of lymphatic disorders. Reportedly, VEGFC/VEGFR3 plays a key role in lymphangiogenesis; moreover, VEGFC/VEGFR3 exerts their cellular effects through activation of Ca2+ signaling in several cell types. Herein, we demonstrated that VEGFC significantly up-regulated LEC proliferation through VEGFR3; moreover, VEGFC/VEGFR3 induced Ca2+ signaling activation. By using online tools, miR-128 and miR-3916 were predicted as candidate upstream miRNAs which might target VEGFC/VEGFR3. As verified using Immunoblotting assays, miR-128 significantly regulated the protein levels of VEGFC/VEGFR3, whereas miR-3916 only slightly modulated VEGFC and VEGFR3 proteins. Contrary to VEGFC, miR-128 overexpression remarkably suppressed LEC proliferation, Ca2+ release and ERK1/2-Akt signaling; moreover, the effect of VEGFC could be partially attenuated by miR-128. In summary, miR-128 interacts with the 3â²-UTR of VEGFC and VEGFR3 to inhibit their expression, thus suppressing LEC proliferation through Ca2+ and ERK1/2-Akt signaling. Taken together, we provided novel experimental basis for miRNA-regulated LEC proliferation through Ca2+ signaling.
Keywords
HUVECS5-bromo-2-deoxyuridineNAADPLECsVEGFRmiR-128nicotinic acid adenine dinucleotide phosphateBrdUProliferationLymphatic endothelial cellHuman umbilical vein endothelial cellsCa2+ signalingVascular endothelial growth factorVascular Endothelial Growth Factor (VEGF)optical densityvascular endothelial growth factor receptor
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Authors
Jie Zhou, Zhiyou He, Le Guo, Jizhang Zeng, Pengfei Liang, Licheng Ren, Minghua Zhang, Pihong Zhang, Xiaoyuan Huang,