Thymosin-β 4 induces angiogenesis in critical limb ischemia mice via regulating Notch/NF-κB pathway
| Autor: | Shumin Lv, Yifei Xu, Jin Dai, Xiqing Rong, Hongwen Cai, Lanzhi Zheng |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A 0301 basic medicine CD31 Notch Angiogenesis Notch signaling pathway NF-κB Cell Line Neovascularization Mice 03 medical and health sciences chemistry.chemical_compound angiogenesis 0302 clinical medicine thymosin-β 4 Ischemia Human Umbilical Vein Endothelial Cells Genetics medicine Animals Humans Viability assay Tube formation Neovascularization Pathologic Receptors Notch Muscles NF-kappa B General Medicine Articles Mice Inbred C57BL Thymosin body regions Disease Models Animal Vascular endothelial growth factor A HEK293 Cells 030104 developmental biology chemistry 030220 oncology & carcinogenesis embryonic structures Cancer research cardiovascular system limb ischemia medicine.symptom Signal Transduction |
| Zdroj: | International Journal of Molecular Medicine |
| ISSN: | 1791-244X 1107-3756 |
| Popis: | Thymosin-β 4 (Tβ4) has been reported to exert a pro-angogenic effect on endothelial cells. However, little is known on the role and underlying mechanisms of Tβ4 on critical limb ischemia (CLI). The present study aimed there-fore to investigate the mechanisms and pro-angiogenic effects of Tβ4 in CLI mice. Tβ4 overexpression lentiviral vector was first transfected into HUVEC and CLI mice model, and inhibitors of Notch pathway (DAPT) and NF-κB pathway (BMS) were also applied to HUVEC and CLI mice. Subsequently, MTT, tube formation and wound healing assays were used to determine the cell viability, angiogenesis and migratory ablity of HUVEC, respectively. Western blotting, reverse transcription, quantitative PCR, immunofluorescence and immunohistochemistry were used to detect the expression of the angiogenesis-related factors angiopoietin-2 (Ang2), TEK receptor tyrosine kinase 2 (tie2), vascular endothelial growth factor A (VEGFA), CD31 and α-smooth muscle actin (α-SMA) and the Notch/NF-κB pathways-related factors NOTCH1 intracellular domain (N1ICD), Notch receptor 3 (Notch3), NF-κB and p65 in HUVEC or CLI mice muscle tissues. The results demonstrated that Tβ4 not only enhanced the cell viability, angiogenesis and migratory ability of HUVEC but also promoted the expression of Ang2, tie2, VEGFA, N1ICD, Notch3, NF-κB, and phosphorylated (p)-p65 in HUVEC. In addition, Tβ4 promoted the expression of CD31, α-SMA Ang2, tie2, VEGFA, N1ICD and p-p65 in CLI mice muscle tissues. Treatment with DAPT and BMS had opposite effects of Tβ4, whereas Tβ4 reversed the effect of DAPT and BMS. The findings from the present study suggested that Tβ4 may promote angiogenesis in CLI mice via regulation of Notch/NF-κB pathways. |
| Databáze: | OpenAIRE |
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