Morphogen signaling by Wnt/β-catenin pathway and microenvironmental alteration in the bone marrow of agricultural pesticide exposure-induced experimental aplastic anemia.
Wnt
aplastic anemia
bone marrow failure
hematopoiesis
pesticides
Journal
Journal of biochemical and molecular toxicology
ISSN: 1099-0461
Titre abrégé: J Biochem Mol Toxicol
Pays: United States
ID NLM: 9717231
Informations de publication
Date de publication:
Sep 2020
Sep 2020
Historique:
revised:
14
03
2020
received:
12
10
2019
accepted:
27
04
2020
medline:
16
5
2020
pubmed:
16
5
2020
entrez:
16
5
2020
Statut:
ppublish
Résumé
The etiologic link between pesticide toxicity and aplastic anemia in agricultural and agro-industrial setting has been frequently reported in epidemiological studies conducted worldwide. Chronic pesticide toxicity causes long-term bone marrow injury and perturbs the normal hematopoietic physiology, including survival of hematopoietic progenitor cells and bone marrow's blood cell forming ability. The purpose of this study is to understand the mechanism of pesticide toxicity-mediated bone marrow aplasia by studying Wnt/β-catenin signaling pathway and microenvironmental stromal components. An agricultural pesticide formulation comprising of cypermethrin, chlorpyriphos, and hexaconazole was used to induce bone marrow aplasia in inbred Swiss albino mice. Marrow failure followed by the onset of aplastic condition was confirmed by pancytopenic peripheral blood and hypocellular bone marrow filled with adipocytes. Significant downregulation of canonical Wnt/β-catenin signaling was identified by expression analysis of Wnt3a, β-catenin, and telomerase reverse transcriptase in the aplastic bone marrow hematopoietic stem/progenitor compartment. Along with signaling deregulation, disruption in both the osteoblastic and vascular stromal components was observed in the pesticide-exposed bone marrow microenvironment when compared to control. In this study, we tried to establish the correlation among disease pathophysiology, signaling deregulation in the hematopoietic cells, and bone marrow microenvironmental alteration during environmental exposure-mediated aplastic hematopoietic catastrophe, which may shed light on the unexplored mechanistic perspective of this fatal blood disease.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e22523Subventions
Organisme : Council for Scientific and Industrial Research (CSIR), Govt. of India
ID : 37(1429)/10/EMRII
Organisme : INSPIRE Fellowship, Dept. of Science and Technology, Govt. of India
ID : INSPIRE Fellowship/DST/2013/283 (IF130354)
Informations de copyright
© 2020 Wiley Periodicals LLC.
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