Dataset Information

Reconstructed Genome-Scale Metabolic Model Characterizes Adaptive Metabolic Flux Changes in Peripheral Blood Mononuclear Cells in Severe COVID-19 Patients.

ABSTRACT: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses a mortal threat to human health. The elucidation of the relationship between peripheral immune cells and the development of inflammation is essential for revealing the pathogenic mechanism of COVID-19 and developing related antiviral drugs. The immune cell metabolism-targeting therapies exhibit a desirable anti-inflammatory effect in some treatment cases. In this study, based on differentially expressed gene (DEG) analysis, a genome-scale metabolic model (GSMM) was reconstructed by integrating transcriptome data to characterize the adaptive metabolic changes in peripheral blood mononuclear cells (PBMCs) in severe COVID-19 patients. Differential flux analysis revealed that metabolic changes such as enhanced aerobic glycolysis, impaired oxidative phosphorylation, fluctuating biogenesis of lipids, vitamins (folate and retinol), and nucleotides played important roles in the inflammation adaptation of PBMCs. Moreover, the main metabolic enzymes such as the solute carrier (SLC) family 2 member 3 (SLC2A3) and fatty acid synthase (FASN), responsible for the reactions with large differential fluxes, were identified as potential therapeutic targets. Our results revealed the inflammation regulation potentials of partial metabolic reactions with differential fluxes and their metabolites. This study provides a reference for developing potential PBMC metabolism-targeting therapy strategies against COVID-19.

SUBMITTER: Tang H

PROVIDER: S-EPMC9604493 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Reconstructed Genome-Scale Metabolic Model Characterizes Adaptive Metabolic Flux Changes in Peripheral Blood Mononuclear Cells in Severe COVID-19 Patients.

Tang Hao H Liu Yanguang Y Ruan Yao Y Ge Lingqiao L Zhang Qingye Q

International journal of molecular sciences 20221017 20

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses a mortal threat to human health. The elucidation of the relationship between peripheral immune cells and the development of inflammation is essential for revealing the pathogenic mechanism of COVID-19 and developing related antiviral drugs. The immune cell metabolism-targeting therapies exhibit a desirable anti-inflammatory effect in some treatment cases. In this study, based on diffe ...[more]

PMID: 36293257

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Project description:Cystinosis metabolic bone disease (CMBD) is an emerging concept in infantile nephropathic cystinosis, patients presenting with bone pains, fractures, and deformations during teenage or early adulthood. The underlying mechanisms remain unclear. Our aim was to explore the pro-inflammatory profile of osteoclastic lineage in cystinotic patients. We obtained blood samples from 14 cystinotic patients and 10 pediatric healthy controls. Peripheral blood mononuclear cells (PBMCs) were isolated and used to explore by RT-qPCR the transcript expression of 8 inflammatory markers (Il-6, Il-8, Il-1β, CXCL1, CCL2/MCP-1, CXCR3, Il-1 Receptor, Il-6 Receptor). In addition, when possible, PBMCs were differentiated into osteoclasts for further experiments. The expression of Il-6, IL-8, CXCR3, and CCL2/MCP-1 was significantly increased in PBMCs from cystinotic patients. We also explored the expression of Il-1 Receptor and Il-6 Receptor, two major pro-osteoclastic signal inducers, in osteoclasts differentiated from PBMCs from controls (N = 3) and patients (N = 4). The expression of IL-1 Receptor (but not IL-6 receptor) was increased in osteoclasts obtained from cystinotic patients.ConclusionThere is an inflammatory profile in PBMCs and osteoclastic lineage in cells obtained from cystinotic patients. CXCR3 and MCP-1 stimulate migration and activation of macrophages, that may explain the previously reported local increased osteoclastogenesis. The osteoclastic overexpression of IL-1 Receptor is a relevant observation in the field since blocking Il-1β signaling has recently been proposed as a novel therapeutic approach to improve muscular wasting in this orphan disease.What is known• Cystinosis metabolic bone disease (CMBD), an emerging concept with unclear underlying mechanisms, induces bone pains, fractures and deformations in patients with cystinosis. • Blocking Il-1β signaling may be a novel therapeutic approach to improve muscular wasting in cystinosis.What is new• There is an inflammatory profile in PBMCs and osteoclastic lineage in cells obtained from cystinotic patients, with an over-expression of IL-1 Receptor in osteoclasts. • We provide another experimental rationale to propose targeted anti-inflammatory therapies in cystinotic patients with severe bone disease.

Dataset Information

Reconstructed Genome-Scale Metabolic Model Characterizes Adaptive Metabolic Flux Changes in Peripheral Blood Mononuclear Cells in Severe COVID-19 Patients.

Publications

Reconstructed Genome-Scale Metabolic Model Characterizes Adaptive Metabolic Flux Changes in Peripheral Blood Mononuclear Cells in Severe COVID-19 Patients.

Similar Datasets

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