The kidney, COVID-19, and the chemokine network: an intriguing trio

Mgbemena

et al. 2020

Cancers

Published transcriptomic data from surgically removed metastatic clear cell renal cell carcinoma samples were analyzed from the genomic fabric paradigm (GFP) perspective to identify the best targets for gene therapy. GFP considers the transcriptome as a multi-dimensional mathematical object constrained by a dynamic set of expression controls and correlations among genes. Every gene in the chest wall metastasis, two distinct cancer nodules, and the surrounding normal tissue of the right kidney was characterized by three independent measures: average expression level, relative expression variation, and expression correlation with each other gene. The analyses determined the cancer-induced regulation, control, and remodeling of the chemokine and vascular endothelial growth factor (VEGF) signaling, apoptosis, basal transcription factors, cell cycle, oxidative phosphorylation, renal cell carcinoma, and RNA polymerase pathways. Interestingly, the three cancer regions exhibited different transcriptomic organization, suggesting that the gene therapy should not be personalized only for every patient but also for each major cancer nodule. The gene hierarchy was established on the basis of gene commanding height, and the gene master regulators DAPK3,TASOR, FAM27C and ALG13 were identified in each profiled region. We delineated the molecular mechanisms by which TASOR overexpression and ALG13 silencing would selectively affect the cancer cells with little consequences for the normal cells.

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 84%

Genomic Fabric Remodeling in Metastatic Clear Cell Renal Cell Carcinoma (ccRCC): A New Paradigm and Proposal for a Personalized Gene Therapy Approach

Mgbemena

et al. 2020

Cancers

Reviews in Medical Virology

“…While it does not transmit normal G-protein mediated signalling messages. 57 Previous studies indicated that ACKR2 limits the infiltration of leucocyte, inflammation, and remodelling of fibrotic tissue following AKI; therefore, avoiding the progression of the disease. 71 Moreover, regarding the preventive role of ACKR2 in limiting kidney injury progression, it might be a promising target for renal inflammatory and fibrotic disease associated with AKI.…”

Section: Cytokine Storm Pathological Inflammation and Covid-19-induced Akimentioning

confidence: 99%

Covid‐19 and kidney injury: Pathophysiology and molecular mechanisms

Ahmadian

Khatibi

Soofiyani

et al. 2020

240

256

The novel coronavirus (SARS-CoV-2) has turned into a life-threatening pandemic disease . About 5% of patients with Covid-19 have severe symptoms including septic shock, acute respiratory distress syndrome, and the failure of several organs, while most of them have mild symptoms. Frequently, the kidneys are involved through direct or indirect mechanisms. Kidney involvement mainly manifests itself as proteinuria and acute kidney injury (AKI). The SARS-CoV-2-induced kidney damage is expected to be multifactorial; directly it can infect the kidney podocytes and proximal tubular cells and based on an angiotensin-converting enzyme 2 (ACE2) pathway it can lead to acute tubular necrosis, protein leakage in Bowman's capsule, collapsing glomerulopathy and mitochondrial impairment. The SARS-CoV-2-driven dysregulation of the immune responses including cytokine storm, macrophage activation syndrome, and lymphopenia can be other causes of the AKI. Organ interactions, endothelial dysfunction, hypercoagulability, rhabdomyolysis, and sepsis are other potential mechanisms of AKI. Moreover, lower oxygen delivery to kidney may cause an ischaemic injury. Understanding the fundamental molecular pathways and pathophysiology of kidney injury and AKI in Covid-19 is necessary to develop management strategies and design effective therapies.

“…They include IL-6, IL-1β, IL-1RA, IL-7, IL-8, IL-9, IL-10, fibroblast growth factor (FGF), GM-CSF, IFN-γ, G-CSF, CXCL10, CCL2, CCL3, PDGF, TNF-α, and VEGF ( 33 , 89 , 123 , 359 ). In particular, elevated IL-6 would cause renal endothelial cells to secrete pro-inflammatory chemokines like CCL14 and CCL2, leading to kidney vascular permeability ( 360 , 361 ). Moreover, IFNs could cause the loss of podocytes and stimulate glomerulosclerosis to promote AKI persistence ( 362 ).…”

Section: Clinical Symptomsmentioning

confidence: 99%

The Role of Cytokines and Chemokines in Severe Acute Respiratory Syndrome Coronavirus 2 Infections

Hsu

Peng

et al. 2022

Front. Immunol.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in countless infections and caused millions of deaths since its emergence in 2019. Coronavirus disease 2019 (COVID-19)-associated mortality is caused by uncontrolled inflammation, aberrant immune response, cytokine storm, and an imbalanced hyperactive immune system. The cytokine storm further results in multiple organ failure and lung immunopathology. Therefore, any potential treatments should focus on the direct elimination of viral particles, prevention strategies, and mitigation of the imbalanced (hyperactive) immune system. This review focuses on cytokine secretions of innate and adaptive immune responses against COVID-19, including interleukins, interferons, tumor necrosis factor-alpha, and other chemokines. In addition to the review focus, we discuss potential immunotherapeutic approaches based on relevant pathophysiological features, the systemic immune response against SARS-CoV-2, and data from recent clinical trials and experiments on the COVID-19-associated cytokine storm. Prompt use of these cytokines as diagnostic markers and aggressive prevention and management of the cytokine storm can help determine COVID-19-associated morbidity and mortality. The prophylaxis and rapid management of the cytokine storm appear to significantly improve disease outcomes. For these reasons, this study aims to provide advanced information to facilitate innovative strategies to survive in the COVID-19 pandemic.