The Anti-Angiogenic Effect of Microbotox on Rosacea Is Due to the Suppressed Secretion of VEGF by Mast Cells Resulting From Internalization of the MRGPRX2 Receptor.
Abstract
[BACKGROUND] Intradermal microdroplet injections of botulinum toxin type-A (BoNT/A) effectively ameliorate rosacea-related angiogenesis, but the mechanism remains unclear.
[OBJECTIVE] To explore the anti-angiogenesis of BoNT/A in the rosacea-like mouse model and to measure the secretion of vascular endothelial growth factor (VEGF) by mast cells.
[METHODS] A rosacea-like mouse model was induced by LL37 in both Mas-related G-protein-coupled receptor B2 conditional knockout (MrgprB2) mice and wild-type (WT) mice, then treated with BoNT/A and/or Apatinib. The abundance of endothelial cells and mast cells in mouse skin was determined using dual immunofluorescence staining. The VEGF levels in supernatants and cell lysates of laboratory of allergic disease 2 (LAD2) mast cells were assessed using reverse transcription quantitative polymerase chain reaction, western blots, and enzyme-linked immunosorbent assay. The effect of conditioned medium (CM) collected from LAD2 on human umbilical vein endothelial cells (HUVECs) was determined using tube formation assays. The number of proliferative cells was confirmed using the 5-ethynyl-2'-deoxyuridine incorporation assays. The effect of BoNT/A on the internalization of Mas-related G-protein-coupled receptor X2 (MRGPRX2) was detected using flow cytometry and immunofluorescence staining.
[RESULTS] LL37-induced rosacea-like skin manifestations were significantly alleviated in MrgprB2 mice compared to WT controls. BoNT/A mitigated the LL37-induced secretion of VEGF by LAD2. The CM from BoNT/A-treated LAD2 inhibited HUVEC proliferation and tube formation. The LAD2 cells co-treated with LL37 and BoNT/A exhibited dramatically enhanced MRGPRX2 internalization.
[CONCLUSION] BoNT/A enhances LL37-mediated MRGPRX2 internalization in mast cells, thereby reducing VEGF secretion and neovascularization and improving facial flushing symptom in rosacea.
[OBJECTIVE] To explore the anti-angiogenesis of BoNT/A in the rosacea-like mouse model and to measure the secretion of vascular endothelial growth factor (VEGF) by mast cells.
[METHODS] A rosacea-like mouse model was induced by LL37 in both Mas-related G-protein-coupled receptor B2 conditional knockout (MrgprB2) mice and wild-type (WT) mice, then treated with BoNT/A and/or Apatinib. The abundance of endothelial cells and mast cells in mouse skin was determined using dual immunofluorescence staining. The VEGF levels in supernatants and cell lysates of laboratory of allergic disease 2 (LAD2) mast cells were assessed using reverse transcription quantitative polymerase chain reaction, western blots, and enzyme-linked immunosorbent assay. The effect of conditioned medium (CM) collected from LAD2 on human umbilical vein endothelial cells (HUVECs) was determined using tube formation assays. The number of proliferative cells was confirmed using the 5-ethynyl-2'-deoxyuridine incorporation assays. The effect of BoNT/A on the internalization of Mas-related G-protein-coupled receptor X2 (MRGPRX2) was detected using flow cytometry and immunofluorescence staining.
[RESULTS] LL37-induced rosacea-like skin manifestations were significantly alleviated in MrgprB2 mice compared to WT controls. BoNT/A mitigated the LL37-induced secretion of VEGF by LAD2. The CM from BoNT/A-treated LAD2 inhibited HUVEC proliferation and tube formation. The LAD2 cells co-treated with LL37 and BoNT/A exhibited dramatically enhanced MRGPRX2 internalization.
[CONCLUSION] BoNT/A enhances LL37-mediated MRGPRX2 internalization in mast cells, thereby reducing VEGF secretion and neovascularization and improving facial flushing symptom in rosacea.
추출된 의학 개체 (NER)
| 유형 | 영어 표현 | 한국어 / 풀이 | UMLS CUI | 출처 | 등장 |
|---|---|---|---|---|---|
| 시술 | botulinum toxin
|
보툴리눔독소 주사 | dict | 1 | |
| 해부 | Mast Cells
|
scispacy | 1 | ||
| 해부 | endothelial cells
|
scispacy | 1 | ||
| 해부 | cell lysates
|
scispacy | 1 | ||
| 해부 | LAD2
→ laboratory of allergic disease 2
|
scispacy | 1 | ||
| 해부 | human umbilical vein endothelial cells
|
scispacy | 1 | ||
| 해부 | HUVECs
→ human umbilical vein endothelial cells
|
scispacy | 1 | ||
| 해부 | tube
|
scispacy | 1 | ||
| 해부 | cells
|
scispacy | 1 | ||
| 해부 | skin
|
scispacy | 1 | ||
| 해부 | HUVEC
|
scispacy | 1 | ||
| 해부 | LAD2 cells
|
scispacy | 1 | ||
| 약물 | BoNT/A
→ botulinum toxin type-A
|
C0006050
botulinum toxin type A
|
scispacy | 1 | |
| 약물 | LL37
|
C1413106
CAMP gene
|
scispacy | 1 | |
| 약물 | Apatinib
|
C2346836
apatinib
|
scispacy | 1 | |
| 약물 | LAD2
→ laboratory of allergic disease 2
|
scispacy | 1 | ||
| 약물 | 5-ethynyl-2'-deoxyuridine
|
C0613970
5-ethynyl-2'-deoxyuridine
|
scispacy | 1 | |
| 약물 | [BACKGROUND] Intradermal microdroplet injections of
|
scispacy | 1 | ||
| 약물 | [OBJECTIVE]
|
scispacy | 1 | ||
| 질환 | type-A
|
scispacy | 1 | ||
| 질환 | allergic disease
|
scispacy | 1 | ||
| 기타 | VEGF
→ vascular endothelial growth factor
|
scispacy | 1 | ||
| 기타 | MRGPRX2 Receptor
|
scispacy | 1 | ||
| 기타 | botulinum toxin type-A
|
scispacy | 1 | ||
| 기타 | BoNT/A
→ botulinum toxin type-A
|
scispacy | 1 | ||
| 기타 | mouse
|
scispacy | 1 | ||
| 기타 | vascular endothelial growth factor
|
scispacy | 1 | ||
| 기타 | LL37
|
scispacy | 1 | ||
| 기타 | wild-type
|
scispacy | 1 | ||
| 기타 | mouse skin
|
scispacy | 1 | ||
| 기타 | Mas-related G-protein-coupled receptor X2
|
scispacy | 1 | ||
| 기타 | MRGPRX2
→ Mas-related G-protein-coupled receptor X2
|
scispacy | 1 | ||
| 기타 | mice
|
scispacy | 1 | ||
| 기타 | LL37-mediated MRGPRX2
|
scispacy | 1 |
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