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VEGF receptor promotes hypoxia-induced hematopoietic progenitor proliferation and differentiation

Year: 2021
Type: preprint
Abstract: Intermittent or chronic hypoxia is associated with morbidity and mortality in many diseases such as obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD), respectively. We found exaggerated inflammation with heightened numbers of inflammatory leukocytes in these patients compared with age-matched controls. Chronically hypoxic mice exhibited similar trend and induced proliferation of hematopoietic stem and progenitor cells (HSPC), precursors of inflammatory leukocytes. Consistently, a transcriptomic analysis of human HSPC exposed to hypoxic conditions revealed elevated expression of genes involved in progenitor mobilization. Additionally, bone marrow cells in mice under hypoxic conditions expressed high amount of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFr) and its target genes in hypoxic conditions. In silico and ChIP experiments demonstrated that HIF-1⍺ binds to the promoter region of VEGFr. These results indicate that VEGF signaling in HSPC is an important mediator of their proliferation and differentiation in hypoxia-induced inflammation and represents a potential therapeutic target to prevent aberrant inflammation in hypoxia-associated diseases.
DOI: 10.21203/rs.3.rs-1000955/v1
Authors: Jonathan Florentin, Scott P. O’Neil, Sathish Babu Vasamsetti, Lee L. Ohayon, Anagha Arunkumar, Samit Ghosh, Jennifer C. Boatz, Justin Sui, Corrine R. Kliment, Stephen Y. Chan, Partha Dutta
Language: English
Subfield: Hematology
Field: Medicine
Open Access status: green
Funders: American Heart Association, Pfizer, United Therapeutics Corporation, Zogenix, National Institutes of Health, National Heart, Lung, and Blood Institute
Awards: G108251326, Molecular Drivers of Vascular Stiffness and Metabolic Dysfunction in HIV-Induced Pulmonary Arterial Hypertension, Hematopoietic stem and progenitor cell relocation and activation in the bone marrow after myocardial infarction, Request for a Nikon A1 confocal microscope, The Role of endothelial cell-specific CX3CR1 in pulmonary hypertension, Mechanisms of myelopoiesis after myocardial infarction, G3470388723, G380270960, G3968006953, Iron-Sulfur Deficiency as a Critical Pathogenic Cause of Pulmonary Hypertension, Mechanisms of Myocardial Infarction-induced insulin resistance, G5486590446, G608324977, G6446453727, Defining the systems biology of the vascular matrix in pulmonary hypertension, G7997686280, G887082497, Defining the Complex Biology of the miR-130/301 Family in Pulmonary Hypertension, G9000037288, G9000063706, G9000072144, G9000084742, G9000124101, G9000195340
OpenAlex ID: W3209211788
Cites: 80
Cited by: 2
Related to: 10