Unveiling the shared genes between systemic sclerosis and lung cancer DOI Creative Commons
Pengfei Pan, Xin Liu, Yun Wang

et al.

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Dec. 18, 2024

The risk of lung cancer is significantly increased in patients with systemic sclerosis (SSc), yet the specific genes underlying this association remain unexplored. Our study aims to identify shared by SSc and cancer. We identified differentially expressed (DEGs) from adenocarcinoma (LUAD) datasets (SSc: GSE95065, LUAD: GSE136043) GEO database. found intersecting top protein–protein interaction networks STRING area under ROC curve (AUC) was calculated for each gene validation GSE231692; GSE43458), identifying PRKG2 as core gene. used UALCAN platform assess expression LUAD at various stages lymph node metastasis states, compared disease-free survival (DFS) between low high groups. overexpressed A549 cells its impact on cell proliferation invasion vitro . seven (SCN7A, AGTR1, WIF1, PRKG2, LTF, AQP4, COL10A1), AUC exceeding 0.93 both diseases (SSc = 0.973; 0.939). levels different clinical states were consistently lower than those observed normal individuals. DFS group higher that ( p 0.028). In experiments confirmed elevated inhibits cells. one cancer, affecting

Language: Английский

Isoform-selective TGF-β3 inhibition for systemic sclerosis DOI Creative Commons
Tianhe Sun, Jason A. Vander Heiden, Xia Gao

et al.

Med, Journal Year: 2024, Volume and Issue: 5(2), P. 132 - 147.e7

Published: Jan. 24, 2024

BackgroundTransforming growth factor β (TGF-β) is implicated as a key mediator of pathological fibrosis, but its pleiotropic activity in range homeostatic functions presents challenges to safe and effective therapeutic targeting. There are three isoforms TGF-β, TGF-β1, TGF-β2, TGF-β3, which bind common receptor complex composed TGF-βR1 TGF-βR2 induce similar intracellular signals vitro. We have recently shown that the cellular expression patterns activation thresholds TGF-β2 TGF-β3 distinct from those TGF-β1 selective short-term inhibition can attenuate fibrosis vivo without promoting excessive inflammation. Isoform-selective TGF-β may therefore provide opportunity for patients with chronic fibrotic disorders.MethodsTranscriptomic profiling skin biopsies systemic sclerosis (SSc) multiple clinical trials was performed evaluate role this disease. Antibody humanization, biochemical characterization, crystallization, pre-clinical experiments were further characterize an anti-TGF-β3 antibody.FindingsIn SSc, uniquely correlated biomarkers signaling disease severity. Crystallographic studies establish structural basis potent monoclonal antibody attenuates effectively at clinically translatable exposures. Toxicology suggest that, opposed pan-TGF-β inhibitors, has favorable safety profile administration.ConclusionWe rationale targeting SSc index.FundingThis study funded by Genentech, Inc.

Language: Английский

Citations

9
PPARG/SPP1/CD44 Signaling Pathway in Alveolar Macrophages: Mechanisms of Lipid Dysregulation and Therapeutic Targets in Idiopathic Pulmonary Fibrosis DOI Creative Commons
Ganggang Li, Yuwei Zhang, Huanyu Jiang

et al.

Heliyon, Journal Year: 2025, Volume and Issue: 11(1), P. e41628 - e41628

Published: Jan. 1, 2025

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease. It characterized by inflammation in the parenchyma interstitium. Given its poor prognosis limited treatment options, understanding underlying molecular mechanisms crucial. Recent evidence suggests that lipid metabolism plays pivotal role IPF pathogenesis, however, precise remain poorly understood. To address this, we analyzed 12 bulk RNA-seq 2 single-cell datasets from GEO database using machine learning approaches. As result, identified four key lipid-related genes-PPARG, SPP1, CASP3, PECAM1-that are expressed across various cell types. Specifically, alveolar macrophages (AMs), observed PPARG was significantly downregulated, while SPP1 highly expressed. Importantly, serves as transcriptional regulator of which turn mediates intercellular signaling via CD44. Based on these findings, propose novel PPARG/SPP1/CD44 pathway AMs, modulates likely contributes to progression IPF. Moreover, network pharmacology analysis several herbal compounds target PPARG, offering potential therapeutic opportunities. In conclusion, findings highlight critical present targets for development future strategies.

Language: Английский

Citations

0
RTN3 regulates collagen biosynthesis and profibrotic macrophage differentiation to promote pulmonary fibrosis via interacting with CRTH2 DOI Creative Commons
Chenyu Wang,

Yaqin Chen,

Hao Huang

et al.

Molecular Medicine, Journal Year: 2025, Volume and Issue: 31(1)

Published: Feb. 19, 2025

Language: Английский

Citations

0
Immunological Features and Potential Biomarkers of Systemic Sclerosis–Associated Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis DOI Creative Commons
Shuai Shao, Siyu Cao, Yusha Chen

et al.

The Clinical Respiratory Journal, Journal Year: 2025, Volume and Issue: 19(4)

Published: March 31, 2025

ABSTRACT Background This study aims to summarize the similarities and differences in immune cell characteristics, potential therapeutic targets between systemic sclerosis‐associated interstitial lung disease (SSc‐ILD) idiopathic pulmonary fibrosis (IPF). Methods included SSc‐ILD SSc‐nonILD patients who were admitted Beijing Chaoyang Hospital April 4th, 2013, June 30th, 2023. Publicly available datasets, including peripheral blood monocular (pbmc) single‐cell data, SSc, pbmc transcriptome SSc‐ILD, IPF tissue data analyzed. Statistical analyses conducted using SPSS R software, employing standard statistical methods bioinformatics packages such as Seurat, DESeq2, enrichR, CellChat. Results The results revealed that CD4+/CD8+ T ratio of was significantly higher than patients. In patients, an elevated also observed progressive group, Treg mature CD4+ cells might cause this change. JAK–STAT pathway cytokine–cytokine receptor interaction activated CD30, CD40, FLT3 signaling pathways found play crucial roles interactions with other among SPA17 a commonly upregulated gene lung, its expression correlating positively severity function progression. Conclusion associate ILD initiation progression; key it. serve pan‐ILD marker associated

Language: Английский

Citations

0
Identification of Hub Genes in Interstitial Lung Disease and their Association With Lung Cancer: An In-Silico Analysis DOI
Sanjukta Dasgupta

Published: Feb. 2, 2024

Background: Interstitial lung disease (ILD), a heterogeneous group of pulmonary disorders often leads to the development cancer (LC). However, association between ILD and LC remains unknown. Through bioinformatics analysis, this study attempted understand overlapping genetic features, pathways discover potential therapeutic drugs for treating both disorders. Methods: To investigate transcriptomic relationship patients, two RNA-seq data (GSE229253 GSE231693) from Gene Expression Omnibus were used. Using R/Bioconductor package we have highlighted altered miRNAs that are involved in also play key role progression ILD. Next, using DGIdb web tool identified drug can target these signatures. Finally, binding affinity was evaluated molecular docking analysis. Results: A total 66 common differentially expressed genes (DEGs) observed patients as compared controls. The co-expression physical interaction DEGs found be 63.80% 13.96%, respectively. MMP13, B3GNT3, CXCL14, CD19, SPP1, EPN3, AQP2, MUC4, AQP5, GRIA1, UBD, CXCR2, MMP7, MUC5B, MMP 11, ITLN2 considered hub genes/core LC. enriched associated with indicate an activation MMP-associated extracellular matrix remodeling doxycycline blinatumomab candidate targeting Conclusion: We investigated possible connections databases, which might useful It is envisioned targeted therapy against mRNA features halt

Language: Английский

Citations

1
Human hypofunctionalNCF1variants promote pulmonary fibrosis in the bleomycin-induced mouse model and patients with systemic sclerosis via expansion of SPP1+monocytes-derived macrophages DOI

Xinran Yuan,

Xiaodong Qin, Kenji Takemoto

et al.

Annals of the Rheumatic Diseases, Journal Year: 2024, Volume and Issue: 84(2), P. 294 - 306

Published: Sept. 19, 2024

We assessed the role of a systemic lupus erythematosus causal hypofunctional variant, neutrophil cytosolic factor 1 (NCF1)-p.Arg90His (p.R90H) substitution, in sclerosis (SSc). Association NCF1-H90 with SSc was performed case-control cohorts, bleomycin (BLM)-treated Ncf1-R90 C57BL/6 wildtype and Ncf1-H90 knock-in (KI) littermates. Peripheral blood mononuclear cell (PBMC) subsets were analysed by cytometry time-of-flight. The allele is associated risk for diffuse cutaneous (dcSSc) Chinese European Americans, lung fibrosis patients (OR=2.09, p=7.96E-10). Low copy number NCF1 Americans (OR=4.33, p=2.60E-2). BLM-treated KI mice demonstrated increased pulmonary fibrosis, exhibiting activated type I interferon signature, elevated Spp1, Ccl2, Arg1, Timp1 Il6 expression, enriched macrophage scores tissues. In longitudinal observation cohort, homozygous H90 at baseline had anti-nuclear antibody titres, anti-topoisomerase seropositivity anti-centromere seronegativity, incidence Gender-Age-lung Physiology index, modified Rodnan Skin Score (mRSS) plasma osteopontin (OPN, SPP1), CCL2, ARG1, TIMP-1 IL-6. These sustained mRSS during follow-up years decreased survival. 0, 2 copies carriage PBMCs exhibited dose-dependent increases profibrotic CD14+CD68+CD11b+Tim3+monocytes. Elevated OPN, CCL2 ARG1 CD68+CD11b+monocyte-derived macrophages from after co-culturing anti-CCL2 antibody. activity development dcSSc via expanding SPP1+MoMs CCL2-dependent manner, contributing to severity both SSc.

Language: Английский

Citations

1
Stratification according to autoantibody status in systemic sclerosis reveals distinct molecular signatures DOI Creative Commons
Bénédicte Rouvière, Christelle Le Dantec, Éléonore Bettacchioli

et al.

Annals of the Rheumatic Diseases, Journal Year: 2024, Volume and Issue: unknown, P. ard - 225925

Published: Oct. 22, 2024

Systemic sclerosis (SSc) is a heterogeneous disease, complicating its management. Its complexity and the insufficiency of clinical manifestations alone to delineate homogeneous patient groups further challenge this task. However, autoantibodies could serve as relevant markers for pathophysiological mechanisms driving disease. Identifying specific immunological based on patients' serological statuses might facilitate deeper understanding diversity

Language: Английский

Citations

1
Case report: Successful use of ruxolitinib to treat interstitial pneumonia as an unusual primary presentation in primary myelofibrosis—two birds with one stone DOI Creative Commons
Pingping Xiao,

Zhi-Gao Dong,

Qingqing Wang

et al.

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Nov. 26, 2024

Interstitial lung disease (ILD) is a rare clinical presentation of primary myelofibrosis (PMF).

Language: Английский

Citations

0
Unveiling the shared genes between systemic sclerosis and lung cancer DOI Creative Commons
Pengfei Pan, Xin Liu, Yun Wang

et al.

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Dec. 18, 2024

The risk of lung cancer is significantly increased in patients with systemic sclerosis (SSc), yet the specific genes underlying this association remain unexplored. Our study aims to identify shared by SSc and cancer. We identified differentially expressed (DEGs) from adenocarcinoma (LUAD) datasets (SSc: GSE95065, LUAD: GSE136043) GEO database. found intersecting top protein–protein interaction networks STRING area under ROC curve (AUC) was calculated for each gene validation GSE231692; GSE43458), identifying PRKG2 as core gene. used UALCAN platform assess expression LUAD at various stages lymph node metastasis states, compared disease-free survival (DFS) between low high groups. overexpressed A549 cells its impact on cell proliferation invasion vitro . seven (SCN7A, AGTR1, WIF1, PRKG2, LTF, AQP4, COL10A1), AUC exceeding 0.93 both diseases (SSc = 0.973; 0.939). levels different clinical states were consistently lower than those observed normal individuals. DFS group higher that ( p 0.028). In experiments confirmed elevated inhibits cells. one cancer, affecting

Language: Английский

Citations

0