Increased expression of hypoxia-induced factor 1α mRNA and its related genes in myeloid blood cells from critically ill COVID-19 patients
| Autor: | Eduardo Ferat-Osorio, Eduardo Peña-Martínez, Niels Wacher-Rodarte, Carlos Mata-Lozano, Constantino López-Macías, César González-Bonilla, Javier Torres, Moisés Mercado, Abraham Majluf, Aldo Ferreira-Hermosillo, Eduardo Vadillo, Guillermo Flores-Padilla, Patricia Piña-Sánchez, Lourdes Basurto-Acevedo, Daniel Marrero-Rodríguez, Keiko Taniguchi-Ponciano, Antonieta Chávez-González, Gloria Silva-Román, Roberto Carvente-Garcia, Renata Saucedo, Francisco Blanco-Favela, Hector Mayani, Claudia Ramírez-Rentería, Sandra Vela-Patiño, Juan Carlos Galan |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Myeloid Coronavirus disease 2019 (COVID-19) Critical Illness critically ill Immunology 030204 cardiovascular system & hematology 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Transcription (biology) medicine Humans Myeloid Cells RNA Messenger 030212 general & internal medicine HIF1α Gene Messenger RNA Reverse Transcriptase Polymerase Chain Reaction Sequence Analysis RNA SARS-CoV-2 business.industry Critically ill COVID-19 scRNAseq General Medicine Hypoxia (medical) Hypoxia-Inducible Factor 1 alpha Subunit Up-Regulation medicine.anatomical_structure immature myeloid cells Female medicine.symptom business Research Article |
| Zdroj: | Annals of Medicine article-version (VoR) Version of Record |
| ISSN: | 1365-2060 0785-3890 |
| DOI: | 10.1080/07853890.2020.1858234 |
| Popis: | Background COVID-19 counts 46 million people infected and killed more than 1.2 million. Hypoxaemia is one of the main clinical manifestations, especially in severe cases. HIF1α is a master transcription factor involved in the cellular response to oxygen levels. The immunopathogenesis of this severe form of COVID-19 is poorly understood. Methods We performed scRNAseq from leukocytes from five critically ill COVID-19 patients and characterized the expression of hypoxia-inducible factor1α and its transcriptionally regulated genes. Also performed metanalysis from the publicly available RNAseq data from COVID-19 bronchoalveolar cells. Results Critically-ill COVID-19 patients show a shift towards an immature myeloid profile in peripheral blood cells, including band neutrophils, immature monocytes, metamyelocytes, monocyte-macrophages, monocytoid precursors, and promyelocytes-myelocytes, together with mature monocytes and segmented neutrophils. May be the result of a physiological response known as emergency myelopoiesis. These cellular subsets and bronchoalveolar cells express HIF1α and their transcriptional targets related to inflammation (CXCL8, CXCR1, CXCR2, and CXCR4); virus sensing, (TLR2 and TLR4); and metabolism (SLC2A3, PFKFB3, PGK1, GAPDH and SOD2). Conclusions The up-regulation and participation of HIF1α in events such as inflammation, immunometabolism, and TLR make it a potential molecular marker for COVID-19 severity and, interestingly, could represent a potential target for molecular therapy.Key messagesCritically ill COVID-19 patients show emergency myelopoiesis.HIF1α and its transcriptionally regulated genes are expressed in immature myeloid cells which could serve as molecular targets.HIF1α and its transcriptionally regulated genes is also expressed in lung cells from critically ill COVID-19 patients which may partially explain the hypoxia related events. |
| Databáze: | OpenAIRE |
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