Impairment of the NKT–STAT1–CXCL9 Axis Contributes to Vessel Fibrosis in Pulmonary Hypertension Caused by Lung Fibrosis

Jandl, Katharina; Marsh, Leigh M.; Mutgan, Ayse Ceren; Crnković, Slaven; Valzano, Francesco; Zabini, Diana; Hoffmann, Júlia; Foris, Vasile; Gschwandtner, Elisabeth; Klepetko, Walter; Prosch, Helmut; Flick, Holger; Brčić, Luka; Kern, Izidor; Heinemann, Ákos; Olschewski, Horst; Kovàcs, Gabór; Kwapiszewska, Grażyna

doi:10.1164/rccm.202201-0142oc

Cited by 23 publications

(10 citation statements)

References 58 publications

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“…CEACAM1 [340], ACSL1 [341], TLR4 [342], ABCA1 [343], TLR5 [344], CYP2D6 [345], JAK2 [346], NOTCH2 [347], DDX3X [348], NCOA4 [349], EGR1 [350], IQGAP2 [351], GCLC (glutamate-cysteine ligase catalytic subunit) [352], VEGFA (vascular endothelial growth factor A) [353], ITGB1 [354], LDLR (low density lipoprotein receptor) [355], TLR6 [316], SIRT1 [356], FGL2 [357], TET2 [358], PHF2 [328], VEGFB (vascular endothelial growth factor B) [359], SELENOM (selenoprotein M) [360], TRPM4 [361], OLFM2 [362] and ATAD3A [363] are thought to be involved in non-alcoholic fatty liver disease. Altered expression of ATOH8 [364], STAT1 [365], ARG1 [366], TLR4 [367], VNN1 [368], ABCA1 [369], IFIH1 [370], PTGS2 [371], F2RL1 [289], CYP2D6 [372], PDK4 [373], RNF213 [374], JAK2 [375], NOTCH2 [376], PDGFC (platelet derived growth factor C) [377], TLR2 [378], CYP1B1 [379], IL1RN [380], GCH1 [381], EGR1 [382], HIF1A [383], PLA2G7 [384], CCR2 [385], GAB1 [386], VEGFA (vascular endothelial growth factor A) [387], OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) [388], OXR1 [389], IRF9 [390], FMR1 [391], LDLR (low density lipoprotein receptor) [392], SIRT1 [393], NOD2 [394], ATP13A3 [395], VCAN (versican) [396], FGL2 [397], TET2 [398], KDM6A [399], KLHL2 [400], CAVIN1 [401], TNFRSF4 [402], PF4 [403], VEGFB (vascular endothelial growth factor B) [330], CCR7 [404], PRDX2 [405], HSPB1 [406], TCF4 […”

Section: Discussionmentioning

confidence: 99%

“…Studies have confirmed that EGR1 [350] and SIRT1 [356] are altered expressed in non-alcoholic fatty liver disease. Previous studies have shown that EGR1 [382], SIRT1 [393], STAT1 [365], HIF1A [383] and IRF9 [390] might influence the prognosis in hypertension. EGR1 [449], SIRT1 [458] and STAT1 [435] are a genes which plays a role in diagnosis of CAD.…”

Section: Discussionmentioning

confidence: 99%

“…EGR1 [304], HIF1A [305], STAT1 [286], hsa-mir-31-5p [549], hsa-mir-365b-3p [550], SREBF1 [551] and FOXP3 [552] might be associated with the prognosis of obesity. EGR1 [382], HIF1A [383], STAT1 [365] and FOXP3 [553] mainly involved in the occurrence of hypertension. Aberrant expression of EGR1 [449], STAT1 [435], hsa-mir-16-5p [554], IRF8 [555] and FOXP3 [556] have been observed in CAD.…”

Section: Discussionmentioning

confidence: 99%

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Identification of novel prognostic targets in coronary artery disease and related complications using bioinformatics and next generation sequencing data analysis

Vastrad¹,

Vastrad²

2023

Preprint

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Coronary artery disease (CAD) is the most common cardiovascular disorder and the leading cause of heart related deaths in world. Increasing molecular targets have been discovered for CAD and CAD - related complications prognosis and therapy. However, there is still an urgent need to identify novel biomarkers. Therefore, we evaluated biomarkers that might help the diagnosis and treatment of CAD and CAD related complications. We searched next generation sequencing (NGS) dataset (GSE202625) and identified differentially expressed genes (DEGs) by comparing CAD and normal control samples using DESeq2. Gene ontology (GO) and pathway enrichment analyses of the DEGs were performed using the g:Profiler online database. The protein protein interaction (PPI) network was plotted with IMEx interactome and visualized using Cytoscape. Module analysis of the PPI network was done using PEWCC1. MiRNA hub gene regulatory network and TF hub gene regulatory network analysis was performed to identify the hub genes, miRNAs and TFs. Receiver operating characteristic (ROC) curve analysis was used to predict the diagnostic effectiveness of the hub genes. A total of 118 DEGs (479 up regulated genes and 479 down regulated genes) were detected. The GO enrichment analysis indicated that the DEGs most significantly enriched in cellular response to stimulus and biosynthetic process. The REACTOME pathway enrichment analysis revealed that the DEGs were most significantly enriched in immune system and eukaryotic translation elongation. PPI network, modules, miRNA hub gene regulatory network and TF hub gene regulatory network analysis demonstrated that EGR1, SIRT1, STAT1, LRRK2, HIF1A, CSNK2B, RPS3, RPS2, RPS4X and HDAC11 were the hub genes. On the whole, the findings of this study enhance our understanding of the potential molecular mechanisms of CAD and CAD-related complications, and provide potential targets for further research.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Identification of novel prognostic targets in coronary artery disease and related complications using bioinformatics and next generation sequencing data analysis

Vastrad¹,

Vastrad²

2023

Preprint

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“…Notably, the depletion of MCs in experimental PAH, as well as inhibition of their activity, attenuates pulmonary vascular remodeling [28][29][30][31] . Regulatory T cells (Tregs), natural killer (NK) cells, and NKT cells appear to play a beneficial role in the maintenance of vascular homeostasis and their deficiency and altered function have been linked to PA remodeling and fibrosis [32][33][34][35] . Experimental and clinical PAH is also accompanied by increased numbers and activation of dendritic cells (DCs) and macrophages in remodeled vessels [10,36,37] .…”

Section: Immune Dysregulation In Phmentioning

confidence: 99%

Immune cell-derived serine protease as pathogenic drivers of vascular remodeling in pulmonary arterial hypertension

Borek¹,

Kwapiszewska²

2023

Rare Dis Orphan Drugs J

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In recent years, accumulating evidence has shown that pulmonary arterial hypertension (PAH) has a strong underlying inflammatory component. Vascular remodeling, a common pathology observed in all forms of pulmonary hypertension (PH), is accompanied by a pronounced accumulation of leukocytes around and within the vessels. Proteolytic products of immune cells, particularly neutrophil and mast cell serine proteases, have been shown to play a central pathogenic role in vascular remodeling and PAH development. Serine proteases are involved in many aspects of the inflammatory response, such as extracellular matrix degradation, regulation of bioavailability of cytokines, chemokines, and growth factors, and dysregulation of their activity can have devastating consequences. In this review, we will focus on immune dysregulation in PAH and shed light on the pro-inflammatory role of serine proteases in vascular pathology observed in the context of this disease.

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“…In this issue of the Journal , Jandl and colleagues (pp. 981–998 ) describe a novel link between natural killer T (NKT) cell deficiency and pulmonary vascular fibrosis ( 7 ). Perivascular type I collagen deposition was increased in lung tissue from patients with PH-ILD, a cohort composed mainly of patients with idiopathic pulmonary fibrosis, chronic hypersensitivity pneumonitis, and unclassified ILD, compared to samples from ILD patients without PH and donor lung controls.…”

mentioning

confidence: 99%

Pulmonary Hypertension Caused by Interstitial Lung Disease: A New iNK(T)ling into Disease Pathobiology

Hersi

Elinoff

2022

Am J Respir Crit Care Med

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Impairment of the NKT–STAT1–CXCL9 Axis Contributes to Vessel Fibrosis in Pulmonary Hypertension Caused by Lung Fibrosis

Cited by 23 publications

References 58 publications

Identification of novel prognostic targets in coronary artery disease and related complications using bioinformatics and next generation sequencing data analysis

Identification of novel prognostic targets in coronary artery disease and related complications using bioinformatics and next generation sequencing data analysis

Immune cell-derived serine protease as pathogenic drivers of vascular remodeling in pulmonary arterial hypertension

Pulmonary Hypertension Caused by Interstitial Lung Disease: A New iNK(T)ling into Disease Pathobiology

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