PUBLICATION
ADAMTS13 protease or lack of von Willebrand factor protects irradiation and melanoma-induced thrombotic microangiopathy in zebrafish
- Authors
- Zheng, L., Cao, L., Zheng, X.L.
- ID
- ZDB-PUB-220728-31
- Date
- 2022
- Source
- Journal of thrombosis and haemostasis : JTH 20(10): 2270-2283 (Journal)
- Registered Authors
- Zheng, Liang
- Keywords
- ADAMTS13, and thrombosis, melanoma, thrombotic microangiopathy, von Willebrand factor
- MeSH Terms
-
- ADAM Proteins
- ADAMTS13 Protein/genetics
- Animals
- Cholesterol
- Fatty Acids
- Melanoma*/genetics
- Phospholipids
- Purpura, Thrombotic Thrombocytopenic*
- RNA
- Steroids
- Thrombotic Microangiopathies*/etiology
- Tumor Microenvironment
- Zebrafish/genetics
- von Willebrand Factor/genetics
- von Willebrand Factor/metabolism
- PubMed
- 35894519 Full text @ J. Thromb. Haemost.
Citation
Zheng, L., Cao, L., Zheng, X.L. (2022) ADAMTS13 protease or lack of von Willebrand factor protects irradiation and melanoma-induced thrombotic microangiopathy in zebrafish. Journal of thrombosis and haemostasis : JTH. 20(10):2270-2283.
Abstract
Background Severe deficiency of plasma ADAMTS13 activity may result in potentially fatal thrombotic thrombocytopenic purpura (TTP) and relative deficiency of plasma ADAMTS13 activity may be associated with adverse outcomes of certain malignancies. Here, we report the role of ADAMTS13 or lack of VWF in irradiation and melanoma-induced thrombotic microangiopathy (TMA) and mortality in zebrafish.
Methods Zebrafish melanoma cell line (ZMEL) was injected subcutaneously into wt, a13-/- , vwf-/- , and a13-/- vwf-/- zebrafish following total body irradiation; the tumor growth, its gene expression pattern, the resulting thrombocytopenia, and mortality were determined.
Results Total body irradiation at 30Gy alone resulted in a transient thrombocytopenia in both wt and a13-/- zebrafish. However, thrombocytopenia occurred earlier and more profound in a13-/- than in wt zebrafish, which was resolved two weeks following irradiation. An inoculation of ZMEL following the irradiation resulted in more severe and persistent thrombocytopenia and earlier death in a13-/- than in wt zebrafish. The vwf-/- or a13-/- vwf-/- zebrafish were protected from developing severe thrombocytopenia following the same maneuvers. RNA-seq revealed significant differentially expressed genes associated with: oxidation-reduction, metabolism, lipid, fatty acid and cholesterol metabolic processes, steroid synthesis, and phospholipid efflux in the melanoma explanted from a13-/- zebrafish compared with that from wt controls.
Conclusions Plasma ADAMTS13 or lack of VWF may offer significant protection against the development of irradiation- and/or melanoma-induced TMA. Such a microenvironment may directly affect melanoma cell phenotypes via alternation of the oxidation-reduction and lipid metabolic pathways.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping