Identification of the shared gene signatures between pulmonary fibrosis and pulmonary hypertension using bioinformatics analysis
Hui Zhao, Lan Wang, Yi Yan, Qin-Hua Zhao, Jing He, Rong Jiang, Ci-Jun Luo, Hong-Ling Qiu, Yu-Qing Miao, Su-Gang Gong, Ping Yuan, Wen-Hui Wu
Frontiers in Immunology, doi:10.3389/fimmu.2023.1197752
Pulmonary fibrosis (PF) and pulmonary hypertension (PH) have common pathophysiological features, such as the significant remodeling of pulmonary parenchyma and vascular wall. There is no effective specific drug in clinical treatment for these two diseases, resulting in a worse prognosis and higher mortality. This study aimed to screen the common key genes and immune characteristics of PF and PH by means of bioinformatics to find new common therapeutic targets. Expression profiles are
Ethics statement The studies involving humans were approved by the Ethics Committee of Shanghai Pulmonary Hospital (numbers: K22-137Y). The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.
Author contributions HZ, LW, and YY investigated the literature research, got the data, and analyzed the data. Q-HZ and JH wrote the article. RJ and C-JL modified the figures. H-LQ and Y-QM revised the article. W-HW, PY, and S-GG conceived the idea of the study, designed the steps of the study, and directed the data analysis. All authors contributed to the article and approved the submitted version.
Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher's note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Supplementary material The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fimmu.2023.1197752/ full#supplementary-material
References
Azuaje, Zhang, Jeanty, Puhl, Rodius et al., Analysis of a gene co-expression network establishes robust association between Col5a2 and ischemic heart disease, BMC Med Genomics,
doi:10.1186/1755-8794-6-13Bilbao, Luciani, Johannesson, Piszczek, Rosenthal, Insulin-like growth factor-1 stimulates regulatory T cells and suppresses autoimmune disease, EMBO Mol Med,
doi:10.15252/emmm.201303376Bindea, Mlecnik, Hackl, Charoentong, Tosolini et al., ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks, Bioinformatics,
doi:10.1093/bioinformatics/btp101Birjandi, Palchevskiy, Xue, Nunez, Kern et al., CD4(+) CD25(hi)Foxp3(+) cells exacerbate bleomycin-induced pulmonary fibrosis, Am J Pathol,
doi:10.1016/j.ajpath.2016.03.020Bloor, Knight, Kedia, Spiteri, Allen, Differential mRNA expression of insulin-like growth factor-1 splice variants in patients with idiopathic pulmonary fibrosis and pulmonary sarcoidosis, Am J Respir Crit Care Med,
doi:10.1164/ajrccm.164.2.2003114Bourgeois, Bonnet, Breuils-Bonnet, Habbout, Paradis et al., Inhibition of CHK 1 (Checkpoint kinase 1) elicits therapeutic effects in pulmonary arterial hypertension, Arterioscler Thromb Vasc Biol,
doi:10.1161/ATVBAHA.119.312537Celada, Kropski, Herazo-Maya, Luo, Creecy et al., PD-1 up-regulation on CD4(+) T cells promotes pulmonary fibrosis through STAT3-mediated IL-17A and TGF-b1 production, Sci Transl Med,
doi:10.1126/scitranslmed.aar8356Chen, Collum, Luo, Weng, Le et al., Macrophage bone morphogenic protein receptor 2 depletion in idiopathic pulmonary fibrosis and Group III pulmonary hypertension, Am J Physiol Lung Cell Mol Physiol,
doi:10.1152/ajplung.00142.2016Chen, Liu, Sun, Zeng, Cai et al., Foxf2 and Smad6 co-regulation of collagen 5A2 transcription is involved in the pathogenesis of intrauterine adhesion, J Cell Mol Med,
doi:10.1111/jcmm.14708Choi, Lee, Sunde, Huizar, Haugk et al., Insulinlike growth factor-I receptor blockade improves outcome in mouse model of lung injury, Am J Respir Crit Care Med,
doi:10.1164/rccm.200802-228OCCollum, Amione-Guerra, As, Difrancesco, Hernandez et al., Pulmonary hypertension associated with idiopathic pulmonary fibrosis: current and future perspectives, Can Respir J,
doi:10.1155/2017/1430350Depianto, Chandriani, Abbas, Jia, 'diaye et al., Heterogeneous gene expression signatures correspond to distinct lung pathologies and biomarkers of disease severity in idiopathic pulmonary fibrosis, Thorax,
doi:10.1136/thoraxjnl-2013-204596Echeverria-Esnal, Martıń-Ontiyuelo, Navarrete-Rouco, Barcelo-Vidal, Conde-Estevez et al., Pharmacological management of antifungal agents in pulmonary aspergillosis: an updated review, Expert Rev Anti Infect Ther,
doi:10.1080/14787210.2021.1962292Formiga, Leblanc, De Souza Reboucas, Farias, De Oliveira et al., Ivermectin: an award-winning drug with expected antiviral activity against COVID-19, J Control Release,
doi:10.1016/j.jconrel.2020.10.009Garibaldi, 'alessio, Mock, Files, Chau et al., Regulatory T cells reduce acute lung injury fibroproliferation by decreasing fibrocyte recruitment, Am J Respir Cell Mol Biol,
doi:10.1165/rcmb.2012-0198OCGilani, Vuga, Lindell, Gibson, Xue et al., CD28 down-regulation on circulating CD4 T-cells is associated with poor prognoses of patients with idiopathic pulmonary fibrosis, PloS One,
doi:10.1371/journal.pone.0008959Grant, Mimche, Paine R 3rd, Liou, Qian et al., Enhanced epithelial sodium channel activity in neonatal Scnn1b mouse lung attenuates high oxygen-induced lung injury, Am J Physiol Lung Cell Mol Physiol,
doi:10.1152/ajplung.00538.2020Hautefort, Girerd, Montani, Cohen-Kaminsky, Price et al., T-helper 17 cell polarization in pulmonary arterial hypertension, Chest,
doi:10.1378/chest.14-1678Humbert, Kovacs, Hoeper, Badagliacca, Berger et al., ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension, Eur Respir J,
doi:10.1183/13993003.00879-2022Ichikawa, Hirahara, Kokubo, Kiuchi, Aoki et al., CD103 (hi) T(reg) cells constrain lung fibrosis induced by CD103(lo) tissue-resident pathogenic CD4 T cells, Nat Immunol,
doi:10.1038/s41590-019-0494-yKotsianidis, Nakou, Bouchliou, Tzouvelekis, Spanoudakis et al., Global impairment of CD4+CD25+FOXP3+ regulatory T cells in idiopathic pulmonary fibrosis, Am J Respir Crit Care Med,
doi:10.1164/rccm.200812-1936OCKundranda, Gracian, Zafar, Meiri, Bendell et al., Randomized, double-blind, placebo-controlled phase II study of istiratumab (MM-141) plus nab-paclitaxel and gemcitabine versus nab-paclitaxel and gemcitabine in front-line metastatic pancreatic cancer (CARRIE), Ann Oncol,
doi:10.1016/j.annonc.2019.09.004Lettieri, Nathan, Barnett, Ahmad, Shorr, Prevalence and outcomes of pulmonary arterial hypertension in advanced idiopathic pulmonary fibrosis, Chest,
doi:10.1378/chest.129.3.746Liu, Huang, Li, Li, Zhang, The cardiac glycoside deslanoside exerts anticancer activity in prostate cancer cells by modulating multiple signaling pathways, Cancers,
doi:10.3390/cancers13225809Liu, Shi, Jiang, Liu, He et al., Regulatory T cellrelated gene indicators in pulmonary hypertension, Front Pharmacol,
doi:10.3389/fphar.2022.908783Lu, Li, Hu, Wang, Expression of immune related genes and possible regulatory mechanisms in Alzheimer's disease, Front Immunol,
doi:10.3389/fimmu.2021.768966Ma, Qin, Zhong, Liao, Su et al., Flavine adenine dinucleotide inhibits pathological cardiac hypertrophy and fibrosis through activating short chain acyl-CoA dehydrogenase, Biochem Pharmacol,
doi:10.1016/j.bcp.2020.114100Martinez, Collard, Pardo, Raghu, Richeldi et al., Idiopathic pulmonary fibrosis, Nat Rev Dis Primers,
doi:10.1038/nrdp.2017.74Meng, Shi, Zeng, Chen, Wu, The role of COL5A2 in patients with muscle-invasive bladder cancer: A bioinformatics analysis of public datasets involving 787 subjects and 29 cell lines, Front Oncol,
doi:10.3389/fonc.2018.00659Milara, Ballester, Morell, Ortiz, Escriváj et al., JAK2 mediates lung fibrosis, pulmonary vascular remodelling and hypertension in idiopathic pulmonary fibrosis: an experimental study, Thorax,
doi:10.1136/thoraxjnl-2017-210728Mirdamadi, Bommhardt, Goihl, Guttek, Zouboulis et al., Insulin and Insulin-like growth factor-1 can activate the phosphoinositide-3-kinase /Akt/FoxO1 pathway in T cells in vitro, Dermatoendocrinol,
doi:10.1080/19381980.2017.1356518Mura, Cecchini, Joseph, Granton, Osteopontin lung gene expression is a marker of disease severity in pulmonary arterial hypertension, Respirology,
doi:10.1111/resp.13557Murphy, Durum, Longo, Human growth hormone promotes engraftment of murine or human T cells in severe combined immunodeficient mice, Proc Natl Acad Sci U.S.A,
doi:10.1073/pnas.89.10.4481Nathan, Waxman, Rajagopal, Case, Johri et al., Inhaled treprostinil and forced vital capacity in patients with interstitial lung disease and associated pulmonary hypertension: a post-hoc analysis of the INCREASE study, Lancet Respir Med,
doi:10.1016/S2213-2600(21)00165-XNo, Imam, Nadeem, Al-Harbi, Korashy et al., Riboflavin attenuates lipopolysaccharide-induced lung injury in rats, Toxicol Mech Methods,
doi:10.3109/15376516.2015.1045662Oherle, Acker, Bonfield, Wang, Gray et al., Insulin-like growth factor 1 supports a pulmonary niche that promotes type 3 innate lymphoid cell development in newborn lungs, Immunity,
doi:10.1016/j.immuni.2020.01.005Pahal, Sharma, Idiopathic Pulmonary Artery Hypertension
Raghu, Amatto, Behr, Stowasser, Comorbidities in idiopathic pulmonary fibrosis patients: a systematic literature review, Eur Respir J,
doi:10.1183/13993003.02316-2014Rajagopal, Bryant, Sahay, Wareing, Zhou et al., Idiopathic pulmonary fibrosis and pulmonary hypertension: Heracles meets the Hydra, Br J Pharmacol,
doi:10.1111/bph.15036Rajkumar, Konishi, Richards, Ishizawar, Wiechert et al., Genomewide RNA expression profiling in lung identifies distinct signatures in idiopathic pulmonary arterial hypertension and secondary pulmonary hypertension, Am J Physiol Heart Circ Physiol,
doi:10.1152/ajpheart.00254.2009Savai, Pullamsetti, Kolbe, Bieniek, Voswinckel et al., Immune and inflammatory cell involvement in the pathology of idiopathic pulmonary arterial hypertension, Am J Respir Crit Care Med,
doi:10.1164/rccm.201202-0335OCSharma, Maclean, Pinto, Kradin, The effect of an anti-CD3 monoclonal antibody on bleomycin-induced lymphokine production and lung injury, Am J Respir Crit Care Med,
doi:10.1164/ajrccm.154.1.8680680Stacher, Graham, Hunt, Gandjeva, Groshong et al., Modern age pathology of pulmonary arterial hypertension, Am J Respir Crit Care Med,
doi:10.1164/rccm.201201-0164OCSun, Ramchandran, Chen, Yang, Raj, Smooth muscle insulin-like growth factor-1 mediates hypoxia-induced pulmonary hypertension in neonatal mice, Am J Respir Cell Mol Biol,
doi:10.1165/rcmb.2015-0388OCTamosiuniene, Manouvakhova, Mesange, Saito, Qian et al., Dominant role for regulatory T cells in protecting females against pulmonary hypertension, Circ Res,
doi:10.1161/CIRCRESAHA.117.312058Tamosiuniene, Tian, Dhillon, Wang, Sung et al., Regulatory T cells limit vascular endothelial injury and prevent pulmonary hypertension, Circ Res,
doi:10.1161/CIRCRESAHA.110.236927Teodoro, De, Queiroz, Santos, Catanozi et al., Proposition of a novel animal model of systemic sclerosis induced by type V collagen in C57BL/6 mice that reproduces fibrosis, vasculopathy and autoimmunity, Arthritis Res Ther,
doi:10.1186/s13075-019-2052-2Tian, Jiang, Jiang, Tamosiuniene, Kim et al., The role of regulatory T cells in pulmonary arterial hypertension, Front Immunol,
doi:10.3389/fimmu.2021.684657Tomaszewski, Bębnowska, Hrynkiewicz, Dworzyński, Niedzẃiedzka-Rystwej et al., Role of the immune system elements in pulmonary arterial hypertension, J Clin Med,
doi:10.3390/jcm10163757Vanderbeke, Janssen, Bergmans, Bourgeois, Buil et al., Posaconazole for prevention of invasive pulmonary aspergillosis in critically ill influenza patients (POSA-FLU): a randomised, open-label, proof-of-concept trial, Intensive Care Med,
doi:10.1007/s00134-021-06431-0Vaz, Hwang, Kagiampakis, Phallen, Patil et al., Chronic cigarette smoke-induced epigenomic changes precede sensitization of bronchial epithelial cells to single-step transformation by KRAS mutations, Cancer Cell,
doi:10.1016/j.ccell.2017.08.006Wang, Lee, Dhandapani, Baek, Kim et al., 8-paradol from ginger exacerbates PINK1/Parkin mediated mitophagy to induce apoptosis in human gastric adenocarcinoma, Pharmacol Res,
doi:10.1016/j.phrs.2022.106610Weigel, Malempati, Reid, Voss, Cho et al., Phase 2 trial of cixutumumab in children, adolescents, and young adults with refractory solid tumors: a report from the Children's Oncology Group, Pediatr Blood Cancer,
doi:10.1002/pbc.24605Wu, Bonnet, Shimauchi, Toro, Grobs et al., Potential for inhibition of checkpoint kinases 1/2 in pulmonary fibrosis and secondary pulmonary hypertension, Thorax,
doi:10.1136/thoraxjnl-2021-217377Yan, Ci, Chen, Chen, Li et al., Anti-inflammatory effects of ivermectin in mouse model of allergic asthma, Inflammation Res,
doi:10.1007/s00011-011-0307-8Yan, He, Jiang, Wang, Chen et al., DNA methyltransferase 3B deficiency unveils a new pathological mechanism of pulmonary hypertension, Sci Adv,
doi:10.1126/sciadv.aba2470Yang, Sun, Ramchandran, Raj, IGF-1 signaling in neonatal hypoxiainduced pulmonary hypertension: Role of epigenetic regulation, Vascul Pharmacol,
doi:10.1016/j.vph.2015.04.005Yao, Zhang, Gao, Wang, Dai et al., Exploration of the shared gene signatures and molecular mechanisms between systemic lupus erythematosus and pulmonary arterial hypertension: evidence from transcriptome data, Front Immunol,
doi:10.3389/fimmu.2021.658341Zeng, Liu, Zhang, Identification of potential biomarkers and immune infiltration characteristics in idiopathic pulmonary arterial hypertension using bioinformatics analysis, Front Cardiovasc Med,
doi:10.3389/fcvm.2021.624714Zhang, Song, Ci, Ju, Li, Ivermectin inhibits LPS-induced production of inflammatory cytokines and improves LPS-induced survival in mice, Inflammation Res,
doi:10.1007/s00011-008-8007-8Zhu, Liu, Hao, Feng, Chen et al., Dietary geranylgeranyl pyrophosphate counteracts the benefits of statin therapy in experimental pulmonary h y p e r t e n s i o n . C i r c u l a t i o n ( 2 0 2 1 ), 1,
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'abstract': '<jats:p>Pulmonary fibrosis (PF) and pulmonary hypertension (PH) have common '
'pathophysiological features, such as the significant remodeling of pulmonary parenchyma and '
'vascular wall. There is no effective specific drug in clinical treatment for these two '
'diseases, resulting in a worse prognosis and higher mortality. This study aimed to screen the '
'common key genes and immune characteristics of PF and PH by means of bioinformatics to find '
'new common therapeutic targets. Expression profiles are downloaded from the Gene Expression '
'Database. Weighted gene co-expression network analysis is used to identify the co-expression '
'modules related to PF and PH. We used the ClueGO software to enrich and analyze the common '
'genes in PF and PH and obtained the protein–protein interaction (PPI) network. Then, the '
'differential genes were screened out in another cohort of PF and PH, and the shared genes '
'were crossed. Finally, RT-PCR verification and immune infiltration analysis were performed on '
'the intersection genes. In the result, the positive correlation module with the highest '
'correlation between PF and PH was determined, and it was found that lymphocyte activation is '
'a common feature of the pathophysiology of PF and PH. Eight common characteristic genes '
'(<jats:italic>ACTR2, COL5A2, COL6A3, CYSLTR1, IGF1, RSPO3, SCARNA17</jats:italic> and '
'<jats:italic>SEL1L</jats:italic>) were gained. Immune infiltration showed that compared with '
'the control group, resting CD4 memory T cells were upregulated in PF and PH. Combining the '
'results of crossing characteristic genes in ImmPort database and RT-PCR, the important gene '
'<jats:italic>IGF1</jats:italic> was obtained. Knocking down <jats:italic>IGF1</jats:italic> '
'could significantly reduce the proliferation and apoptosis resistance in pulmonary '
'microvascular endothelial cells, pulmonary smooth muscle cells, and fibroblasts induced by '
'hypoxia, platelet-derived growth factor-BB (PDGF-BB), and transforming growth factor-β1 '
'(TGF-β1), respectively. Our work identified the common biomarkers of PF and PH and provided a '
'new candidate gene for the potential therapeutic targets of PF and PH in the future.</jats:p>',
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'induce apoptosis in human gastric adenocarcinoma',
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