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Thalidomide Inhibits Angiogenesis via Downregulation of VEGF and Angiopoietin-2 in Crohn's Disease.
- Source :
-
Inflammation [Inflammation] 2021 Apr; Vol. 44 (2), pp. 795-807. Date of Electronic Publication: 2020 Nov 18. - Publication Year :
- 2021
-
Abstract
- Immune-mediated angiogenesis is important in the pathogenesis of inflammatory bowel disease and targeted treatment could alleviate the disease. Thalidomide is an effective drug in inflammatory bowel disease, which might be related to its multiple role in anti-inflammatory, immunoregulatory, and anti-angiogenesis. This study is to investigate the effect of thalidomide on angiogenesis in tissues from patients and in vitro cells. Angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), VEGF, and CD31 expressions in intestinal mucosa from pediatric CD patients before and after thalidomide treatment were measured by immunohistochemistry. Western blotting and polymerase chain reaction were performed to characterize the change of angiogenic factors before and after treatment in remission. Human umbilical vein endothelial cells (HUVECs) treated by thalidomide were used to examine its effect on endothelial cell proliferation and migration and capillary-like structures. Results showed that VEGF and Ang-2 levels were significantly greater in CD patients over controls. Thalidomide produced a significant reduction in protein expression of Ang-2 and VEGF, along with a decrease in mRNA expression of Ang-2. While, Ang-1 level did not show a statistically significant change. Thalidomide significantly inhibited cell proliferation in a dose-dependent manner. It also suppressed VEGF- and Ang-2-induced cell migration and capillary-like tube formation in HUVECs. Therefore, our study suggests that VEGF and Ang-2 levels are up-regulated in pediatric CD patients. It also indicated that thalidomide can be able to deactivate endothelium by the downregulation effect on angiogenic factors by targeting VEGF and Ang-2.
- Subjects :
- Adolescent
Angiogenesis Inhibitors pharmacology
Biomarkers metabolism
Blotting, Western
Case-Control Studies
Child
Child, Preschool
Crohn Disease metabolism
Down-Regulation drug effects
Female
Human Umbilical Vein Endothelial Cells drug effects
Human Umbilical Vein Endothelial Cells metabolism
Humans
Immunohistochemistry
Infant
Intestinal Mucosa blood supply
Intestinal Mucosa drug effects
Intestinal Mucosa metabolism
Male
Neovascularization, Pathologic drug therapy
Neovascularization, Pathologic metabolism
Real-Time Polymerase Chain Reaction
Retrospective Studies
Thalidomide pharmacology
Treatment Outcome
Angiogenesis Inhibitors therapeutic use
Angiopoietin-2 metabolism
Crohn Disease drug therapy
Thalidomide therapeutic use
Vascular Endothelial Growth Factor A metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1573-2576
- Volume :
- 44
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Inflammation
- Publication Type :
- Academic Journal
- Accession number :
- 33206273
- Full Text :
- https://doi.org/10.1007/s10753-020-01378-8