Expression profiling of inflammation-related genes including IFI-16, NOTCH2, CXCL8, THBS1 in COVID-19 patients

Hamldar, Shahrzad; Kiani, Seyed Jalal; Khoshmirsafa, Majid; Nahand, Javid Sadri; Mirzaei, Hamed; Khatami, Alireza; Kahyesh‐Esfandiary, Roya; Khanaliha, Khadijeh; Tavakoli, Ahmad; Bokharaei-Salim, Farah

doi:10.1016/j.biologicals.2022.09.001

Cited by 6 publications

(5 citation statements)

References 33 publications

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“…Despite the SARS-CoV-2 samples showing undetectable SARS-CoV-2 by RNA-scope, transcriptional profiling showed positive enrichment of SARS-CoV-2 related pathways in the SARS-CoV-2 samples, such as “SARS_COV_2_INFECTION”, and “SARS_COV_2_HOST_INTERACTIONS” from the Reactome database, as well as the Interferon Alpha Response pathway from the Hallmark database, which is a first-line immune response pathway that has been associated with SARS-CoV-2 infection (Figure 2d-f) 15 . These pathways were supported by increased expression of genes that have been associated with SARS-CoV-2, such as the inflammatory marker IFI16 16 , disease progression marker IFI27 17 , disease prognosticator B2M 18 , activation of Janus Kinases (i.e., JAK1 ), and expression of STAT3 19 (Figure 2 g-j). Notably, gene expression for these markers was elevated predominantly in the villous core stroma cell compartment, presumably stemming from the immune subpopulation within the stroma.…”

Section: Resultsmentioning

confidence: 87%

“…with SARS-CoV-2, such as the inflammatory marker IFI16 16 , disease progression marker IFI27 17 , disease prognosticator B2M 18 , activation of Janus Kinases (i.e., JAK1), and expression of STAT3 19 (Figure 2 g-j). Notably, gene expression for these markers was elevated predominantly in the villous core stroma cell compartment, presumably stemming from the immune subpopulation within the stroma.…”

Section: Sars-cov-2 Infection Related Pathways Enriched In the Placen...mentioning

confidence: 99%

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Whole transcriptome profiling of placental pathobiology in SARS-CoV-2 pregnancies identifies placental dysfunction signatures

Stylianou

Sebina

Matigian³

et al. 2023

Preprint

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Pregnant people infected with the SARS-CoV-2 virus have shown a higher incidence of "preeclampsia-like syndrome". Preeclampsia is a systematic syndrome that affects 5% of people worldwide and is the leading cause of maternal mortality. It is characterised by placental dysfunction, leading to poor placental perfusion, maternal hypertension and neurological disturbances. Here, we used whole-transcriptome, spatial profiling of placental tissues to analyse the expression of genes between placentae from pregnant participants who contracted SARS-CoV-2 and those prior to the pandemic. Our analysis of the trophoblast and villous core stromal cell populations revealed tissue-specific pathways enriched in the SARS-CoV-2 placentae that align with a pre-eclampsia signature. Most notably, we found enrichment of pathways involved in vascular tension, blood pressure, inflammation, and oxidative stress. This study illustrates how spatially resolved transcriptomic analysis can aid in understanding the underlying pathogenic mechanisms of SARS-CoV-2 in pregnancy that are thought to induce "preeclampsia-like syndrome". Our study highlights the benefits of spatial profiling to map the crosstalk between trophoblast and villous core stromal cells linked to pathways involved in "preeclampsia-like syndrome."

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Section: Resultsmentioning

confidence: 87%

Section: Sars-cov-2 Infection Related Pathways Enriched In the Placen...mentioning

confidence: 99%

Whole transcriptome profiling of placental pathobiology in SARS-CoV-2 pregnancies identifies placental dysfunction signatures

Stylianou

Sebina

Matigian³

et al. 2023

Preprint

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“…Rel −/− mice had a significantly reduced T-cell proliferative response to the virus and attenuated local and systemic influenza virus-specific antibody responses, with normal levels of virus-specific cytotoxic T lymphocytes, which were able to clear the virus from the mouse lungs [ 120 ]. Thbs1 (thrombospondin 1) is released and increased during the acute phase of inflammation and plays a synergistic role in the inflammatory process; Thbs1 is a pro-inflammatory factor [ 120 ], which was increased among COVID-19 patients [ 121 ].…”

Section: Resultsmentioning

confidence: 99%

Preclinical Study in Mouse Thymus and Thymocytes: Effects of Treatment with a Combination of Sodium Dichloroacetate and Sodium Valproate on Infectious Inflammation Pathways

Stakišaitis,

Kapočius,

Kilimaitė

et al. 2023

Pharmaceutics

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The research presents data from a preclinical study on the anti-inflammatory effects of a sodium dichloroacetate and sodium valproate combination (DCA–VPA). The 2-week treatment with a DCA 100 mg/kg/day and VPA 150 mg/kg/day combination solution in drinking water’s effects on the thymus weight, its cortex/medulla ratio, Hassall’s corpuscles (HCs) number in the thymus medulla, and the expression of inflammatory and immune-response-related genes in thymocytes of male Balb/c mice were studied. Two groups of mice aged 6–7 weeks were investigated: a control (n = 12) and a DCA–VPA-treated group (n = 12). The treatment did not affect the body weight gain (p > 0.05), the thymus weight (p > 0.05), the cortical/medulla ratio (p > 0.05), or the number of HCs (p > 0.05). Treatment significantly increased the Slc5a8 gene expression by 2.1-fold (p < 0.05). Gene sequence analysis revealed a significant effect on the expression of inflammation-related genes in thymocytes by significantly altering the expression of several genes related to the cytokine activity pathway, the inflammatory response pathway, and the Il17 signaling pathway in thymocytes. Data suggest that DCA–VPA exerts an anti-inflammatory effect by inhibiting the inflammatory mechanisms in the mouse thymocytes.

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“…Despite the SARS-CoV-2 samples showing undetectable SARS-CoV-2 by RNA-scope, transcriptional profiling showed positive enrichment of SARS-CoV-2 related pathways in the SARS-CoV-2 samples, such as 'SARS_COV_2_INFECTION', and 'SARS_COV_2_HOST_INTERACTIONS' from the Reactome database, as well as the Interferon Alpha Response pathway from the Hallmark database, which is a first-line immune response pathway that has been associated with SARS-CoV-2 infection (Figure 2d-f). 15 These pathways were supported by increased expression of genes that have been associated with SARS-CoV-2, such as the inflammatory marker IFI16, 16 disease progression marker IFI27, 17 disease prognosticator B2M, 18 activation of Janus Kinases (i.e. JAK1), and expression of STAT3 19 (Figure 2g-j).…”

Section: Sars-cov-2 Infection Related Pathways Enriched In the Placen...mentioning

confidence: 92%

Whole transcriptome profiling of placental pathobiology in SARS‐CoV‐2 pregnancies identifies placental dysfunction signatures

Stylianou,

Sebina,

Matigian

et al. 2024

Clin & Trans Imm

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ObjectivesSevere Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) virus infection in pregnancy is associated with higher incidence of placental dysfunction, referred to by a few studies as a ‘preeclampsia‐like syndrome’. However, the mechanisms underpinning SARS‐CoV‐2‐induced placental malfunction are still unclear. Here, we investigated whether the transcriptional architecture of the placenta is altered in response to SARS‐CoV‐2 infection.MethodsWe utilised whole‐transcriptome, digital spatial profiling, to examine gene expression patterns in placental tissues from participants who contracted SARS‐CoV‐2 in the third trimester of their pregnancy (n = 7) and those collected prior to the start of the coronavirus disease 2019 (COVID‐19) pandemic (n = 9).ResultsThrough comprehensive spatial transcriptomic analyses of the trophoblast and villous core stromal cell subpopulations in the placenta, we identified SARS‐CoV‐2 to promote signatures associated with hypoxia and placental dysfunction. Notably, genes associated with vasodilation (NOS3), oxidative stress (GDF15, CRH) and preeclampsia (FLT1, EGFR, KISS1, PAPPA2) were enriched with SARS‐CoV‐2. Pathways related to increased nutrient uptake, vascular tension, hypertension and inflammation were also enriched in SARS‐CoV‐2 samples compared to uninfected controls.ConclusionsOur findings demonstrate the utility of spatially resolved transcriptomic analysis in defining the underlying pathogenic mechanisms of SARS‐CoV‐2 in pregnancy, particularly its role in placental dysfunction. Furthermore, this study highlights the significance of digital spatial profiling in mapping the intricate crosstalk between trophoblasts and villous core stromal cells, thus shedding light on pathways associated with placental dysfunction in pregnancies with SARS‐CoV‐2 infection.

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Expression profiling of inflammation-related genes including IFI-16, NOTCH2, CXCL8, THBS1 in COVID-19 patients

Cited by 6 publications

References 33 publications

Whole transcriptome profiling of placental pathobiology in SARS-CoV-2 pregnancies identifies placental dysfunction signatures

Whole transcriptome profiling of placental pathobiology in SARS-CoV-2 pregnancies identifies placental dysfunction signatures

Preclinical Study in Mouse Thymus and Thymocytes: Effects of Treatment with a Combination of Sodium Dichloroacetate and Sodium Valproate on Infectious Inflammation Pathways

Whole transcriptome profiling of placental pathobiology in SARS‐CoV‐2 pregnancies identifies placental dysfunction signatures

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