VEGF Receptor 1 Promotes Hypoxia-Induced Hematopoietic Progenitor Proliferation and Differentiation.

Autor:	Florentin J; Division of Cardiology, Department of Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States., O'Neil SP; Division of Cardiology, Department of Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States., Ohayon LL; Division of Cardiology, Department of Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States., Uddin A; Division of Cardiology, Department of Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States., Vasamsetti SB; Division of Cardiology, Department of Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States., Arunkumar A; Division of Cardiology, Department of Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States., Ghosh S; Department of Medicine, Division of Pulmonary and Critical Care, University of Pittsburgh, Pittsburgh, PA, United States., Boatz JC; Department of Medicine, Division of Pulmonary and Critical Care, University of Pittsburgh, Pittsburgh, PA, United States., Sui J; Department of Medicine, Division of Pulmonary and Critical Care, University of Pittsburgh, Pittsburgh, PA, United States., Kliment CR; Department of Medicine, Division of Pulmonary and Critical Care, University of Pittsburgh, Pittsburgh, PA, United States., Chan SY; Division of Cardiology, Department of Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States., Dutta P; Division of Cardiology, Department of Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 May 12; Vol. 13, pp. 882484. Date of Electronic Publication: 2022 May 12 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.882484
Abstrakt:	Although it is well known that hypoxia incites unleashed cellular inflammation, the mechanisms of exaggerated cellular inflammation in hypoxic conditions are not known. We observed augmented proliferation of hematopoietic stem and progenitor cells (HSPC), precursors of inflammatory leukocytes, in mice under hypoxia. Consistently, a transcriptomic analysis of human HSPC exposed to hypoxic conditions revealed elevated expression of genes involved in progenitor proliferation and differentiation. Additionally, bone marrow cells in mice expressed high amount of vascular endothelial growth factor (VEGF), and HSPC elevated VEGF receptor 1 (VEGFr1) and its target genes in hypoxic conditions. In line with this, VEGFr1 blockade in vivo and in vitro decreased HSPC proliferation and attenuated inflammation. In silico and ChIP experiments demonstrated that HIF-1α binds to the promoter region of VEGFR1 . Correspondingly, HIF1a silencing decreased VEGFr1 expression in HSPC and diminished their proliferation. 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. Competing Interests: SYC has served as a consultant for Zogenix, Aerpio, and United Therapeutics. SYC holds research grants from Actelion and Pfizer. SYC has filed patent applications regarding the targeting of metabolism in pulmonary hypertension. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Florentin, O’Neil, Ohayon, Uddin, Vasamsetti, Arunkumar, Ghosh, Boatz, Sui, Kliment, Chan and Dutta.)
Databáze:	MEDLINE
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