Fli1 deficiency induces endothelial adipsin expression, contributing to the onset of pulmonary arterial hypertension in systemic sclerosis

Miyagawa, Takuya; Taniguchi, Takashi; Saigusa, Ryosuke; Fukayama, Masahisa; Takahashi, Takehiro; Yamashita, Takashi; Hirabayashi, Megumi; Miura, Shunsuke; Nakamura, Kouki; Yoshizaki, Ayumi; Sato, Shinichi; Asano, Yoshihide

doi:10.1093/rheumatology/kez517

Cited by 15 publications

(12 citation statements)

References 46 publications

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“…It has been proposed that EC phenotypic changes contribute to the onset of PAH, e.g. in the cases of smoking-induced lung EC apoptosis or inherited epigenetic EC dysfunction [18][19][20]. However, dysfunctional EC phenotypes can manifest in parallel with PAH or after the onset of PAH, e.g.…”

Section: Introductionmentioning

confidence: 99%

Endothelial cells in the pathogenesis of pulmonary arterial hypertension

et al. 2021

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Pulmonary arterial hypertension (PAH) is a devastating disease that involves pulmonary vasoconstriction, small vessel obliteration, large vessel thickening and obstruction, and development of plexiform lesions. PAH vasculopathy leads to progressive increases in pulmonary vascular resistance, right heart failure, and ultimately, premature death. Besides other cell types that are known to be involved in PAH pathogenesis (e.g. smooth muscle cells, fibroblasts, and leukocytes), recent studies demonstrate a crucial role of endothelial cells (ECs) in the initiation and progression of PAH. The EC-specific role in PAH is multi-faceted and impacts upon numerous pathophysiological processes including vasoconstriction, inflammation, coagulation, metabolism, and oxidative/nitrative stress, as well as cell viability, growth, and differentiation. In this review, we describe how EC dysfunction and cell signalling regulate the pathogenesis of PAH. We also highlight areas of research that warrant attention in future studies, and discuss potential molecular signalling pathways in ECs that could be targeted therapeutically in the prevention and treatment of PAH.

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Section: Introductionmentioning

confidence: 99%

Endothelial cells in the pathogenesis of pulmonary arterial hypertension

et al. 2021

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“…BMI1 [245], CCL5 [246], GREM1 [247], ANGPTL3 [248], ARG2 [249], MSRA (methionine sulfoxidereductase A) [250], SNCA (synuclein alpha) [251], NOX4 [252], PFKFB2 [253], PDZK1 [254], SUCNR1 [255], LYVE1 [256], AZGP1 [257], ERBB4 [258] and PLAT (plasminogen activator, tissue type) [259] might serve as molecular markers for kidney fibrosis. BMI1 [260], IGF2 [261], IRF7 [262], CCL5 [263], ACTN3 [264], E2F1 [265], PF4 [266], TEAD4 [267], TBX4 [268], GREM1 [269], CYP11B2 [270], WNT3A [124], COMP (cartilage oligomeric matrix protein) [271], FLI1 [272], RAP1B [273], ANGPTL3 [274], CYP3A5 [275], HSD11B2 [276], HMGCS2 [277], AGXT2 [278], SLC22A12 [279], FGF1 [280], CRY1 [281], PPARGC1A [282], SLC19A3 [283], CYP2C8 [284], ACOX2 [285], SLC2A9 [286], MSRA (methionine sulfoxidereductase A) [287], VNN1 [288], EPHX2 [289], CROT (carnitine O-octanoyltransferase) [290], SCNN1B [291], NR4A3 [292], HSD17B7 [293], SLC22A2 [294], AQP2 [295], SLC2A2 [296], EGF (epidermal growth factor) [297], ANGPT1 [298], SLC26A4 [299], KL (klotho) [300], SCNN1G [301], PDZK1 [302], PTPRD (protein tyrosine phosphatase receptor type D) [303], ACE2 [304], FOLH1 [305], SUCNR1 [306], GLCE (glucuronic acid epimerase) [307], AQP3 [308], DPP4 [309], REN (renin) [310], TRPM6 [311], ABCB1 [312], MTTP (microsomal triglyceride transfer protein) [313], CALCRL (calcitonin receptor like receptor) [314], ENPEP (glutamylaminopept...…”

Section: Discussionmentioning

confidence: 99%

Identification of novel prognostic targets in acute kidney injury using bioinformatics and next generation sequencing data analysis

Vastrad,

Vastrad

2024

Preprint

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Acute kidney injury (AKI) is a type of renal disease occurs frequently in hospitalized patients, which may cause abnormal renal function and structure with increase in serum creatinine level with or without reduced urine output. With the incidence of AKI is increasing. However, the molecular mechanisms of AKI have not been elucidated. It is significant to further explore the molecular mechanisms of AKI. We downloaded the GSE139061 next generation sequencing (NGS) dataset from the Gene Expression Omnibus (GEO) database. Limma R bioconductor package was used to screen the differentially expressed genes (DEGs). Then, the enrichment analysis of DEGs in Gene Ontology (GO) function and REACTOME pathways was analyzed by g:Profiler. Next, the protein-protein interaction (PPI) network and modules was constructed and analyzed, and the hub genes were identified. Next, the miRNA-hub gene regulatory network and TF-hub gene regulatory network were built. We also validated the identified hub genes via receiver operating characteristic (ROC) curve analysis. Overall, 956 DEGs were identified, including 478 up regulated and 478 down regulated genes. The enrichment functions and pathways of DEGs involve primary metabolic process, small molecule metabolic process, striated muscle contraction and metabolism. Topological analysis of the PPI network and module revealed that hub genes, including PPP1CC, RPS2, MDFI, BMI1, RPL23A, VCAM1, ALB, SNCA, DPP4 and RPL26L1, might be involved in the development of AKI. miRNA-hub gene and TF-hub gene regulatory networks revealed that miRNAs and TFs including hsa-mir-510-3p, hsa-mir-6086 and mir-146a-5p, MAX and PAX2, might be involved in the development of AKI. Various known and newtherapeutic targets were obtained via network analysis. The results of the current investigation might be beneficial for the diagnosis and treatment of AKI.

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“…Heart involvement was defined as symptomatic pericarditis, clinical evidence of left ventricular congestive heart failure, and/or arrhythmias requiring treatment. Elevated right ventricular systolic pressure (RVSP) was defined as 35 mm Hg or more on echocardiogram 20‐23 . Arthropathy was clinically assessed, including complaints of joint stiffness or arthralgia, and objectively swollen joints.…”

Section: Methodsmentioning

confidence: 99%

Association of serum CXCL12 levels with arthropathy in patients with systemic sclerosis

et al. 2020

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Aim Systemic sclerosis (SSc) is an autoimmune connective tissue disease, in which extensive fibrotic change and vasculopathy affect the skin and various internal organs. It also involves the joints, causing stiffness, arthralgia, and arthritis. Although arthropathy is commonly observed in SSc, its underlying mechanism remains unknown. CXCL12, also known as stromal cell derived factor 1, is associated with inflammation, mesenchymal cell recruitment, angiogenesis, and collagen production, and is implicated in the development of various joint diseases. To assess the potential contribution of CXCL12 to SSc development, we investigated the clinical association of serum CXCL12 levels in patients with SSc. Method We conducted a cross‐sectional analysis of 68 patients with SSc and 20 healthy controls recruited in a single center over 9 years. Serum CXCL12 levels were measured by enzyme‐linked immunosorbent assay. Results Serum CXCL12 levels were significantly higher in patients with SSc than in healthy controls (median 1554.0 pg/mL, 25th‐75th centiles 1313.0‐1914.0 pg/mL vs 967.4 pg/mL, 608.8‐1271.0 pg/mL, P < 0.001). Patients with SSc with elevated CXCL12 levels had significantly more cases of arthropathy than those with normal CXCL12 levels (85.7% vs 25.0%, P = 0.01). Furthermore, patients with SSc with elevated CXCL12 levels showed an increased trend in the prevalence of limited range of motion of the finger joints compared with those with normal CXCL12 levels (60.0% vs 18.6%, P =0 .07). Moreover, serum CXCL12 levels were significantly correlated with the titers of rheumatoid factor in patients with SSc (r = .41, P = 0.001). Conclusion Elevated serum CXCL12 levels may be related to the development of SSc arthropathy.

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Fli1 deficiency induces endothelial adipsin expression, contributing to the onset of pulmonary arterial hypertension in systemic sclerosis

Cited by 15 publications

References 46 publications

Endothelial cells in the pathogenesis of pulmonary arterial hypertension

Endothelial cells in the pathogenesis of pulmonary arterial hypertension

Identification of novel prognostic targets in acute kidney injury using bioinformatics and next generation sequencing data analysis

Association of serum CXCL12 levels with arthropathy in patients with systemic sclerosis

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