Microarray-based Detection of Critical Overexpressed Genes in the Progression of Hepatic Fibrosis in Non-alcoholic Fatty Liver Disease: A Protein-protein Interaction Network Analysis


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Abstract

Background:Non-alcoholic fatty liver disease (NAFLD) is a prevalent cause of chronic liver disease and encompasses a broad spectrum of disorders, including simple steatosis, steatohepatitis, fibrosis, cirrhosis, and liver cancer. However, due to the global epidemic of NAFLD, where invasive liver biopsy is the gold standard for diagnosis, it is necessary to identify a more practical method for early NAFLD diagnosis with useful therapeutic targets; as such, molecular biomarkers could most readily serve these aims. To this end, we explored the hub genes and biological pathways in fibrosis progression in NAFLD patients.

Methods:Raw data from microarray chips with GEO accession GSE49541 were downloaded from the Gene Expression Omnibus database, and the R package (Affy and Limma) was applied to investigate differentially expressed genes (DEGs) involved in the progress of low- (mild 0-1 fibrosis score) to high- (severe 3-4 fibrosis score) fibrosis stage NAFLD patients. Subsequently, significant DEGs with pathway enrichment were analyzed, including gene ontology (GO), KEGG and Wikipathway. In order to then explore critical genes, the protein-protein interaction network (PPI) was established and visualized using the STRING database, with further analysis undertaken using Cytoscape and Gephi software. Survival analysis was undertaken to determine the overall survival of the hub genes in the progression of NAFLD to hepatocellular carcinoma.

Results:A total of 311 significant genes were identified, with an expression of 278 being upregulated and 33 downregulated in the high vs. low group. Gene functional enrichment analysis of these significant genes demonstrated major involvement in extracellular matrix (ECM)-receptor interaction, protein digestion and absorption, and the AGE-RAGE signaling pathway. The PPI network was constructed with 196 nodes and 572 edges with PPI enrichment using a p-valup < 0.0 e-16. Based on this cut-off, we identified 12 genes with the highest score in four centralities: Degree, Betweenness, Closeness, and Eigenvector. Those twelve hub genes were CD34, THY1, CFTR, COL3A1, COL1A1, COL1A2, SPP1, THBS1, THBS2, LUM, VCAN, and VWF. Four of these hub genes, namely CD34, VWF, SPP1, and VCAN, showed significant association with the development of hepatocellular carcinoma.

Conclusions:This PPI network analysis of DEGs identified critical hub genes involved in the progression of fibrosis and the biological pathways through which they exert their effects in NAFLD patients. Those 12 genes offer an excellent opportunity for further focused research to determine potential targets for therapeutic applications.

About the authors

Ali Mahmoudi

Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences

Email: info@benthamscience.net

Alexandra Butler

, Royal College of Surgeons in Ireland Bahrain

Email: info@benthamscience.net

Antonio De Vincentis

Unit of Internal Medicine and Geriatrics, Università Campus Bio-Medico di Roma, Fondazione Policlinico Universitario Campus Bio-Medico di Roma

Email: info@benthamscience.net

Tannaz Jamialahmadi

Applied Biomedical Research Center, Mashhad University of Medical Sciences

Email: info@benthamscience.net

Amirhossein Sahebkar

Applied Biomedical Research Cente, Mashhad University of Medical Sciences

Author for correspondence.
Email: info@benthamscience.net

References

  1. Al-Qarni, R.; Iqbal, M.; Al-Otaibi, M.; Al-Saif, F.; Alfadda, A.A.; Alkhalidi, H.; Bamehriz, F.; Hassanain, M. Validating candidate biomarkers for different stages of non-alcoholic fatty liver disease. Medicine, 2020, 99(36), e21463. doi: 10.1097/MD.0000000000021463 PMID: 32898995
  2. Pellicano, A.J.; Spahn, K.; Zhou, P.; Goldberg, I.D.; Narayan, P. Collagen characterization in a model of nonalcoholic steatohepatitis with fibrosis; a call for development of targeted therapeutics. Molecules, 2021, 26(11), 3316. doi: 10.3390/molecules26113316 PMID: 34205850
  3. Romualdo, G.R.; Da Silva, T.C.; Landi, M.F.; Morais, J.Á.; Barbisan, L.F.; Vinken, M.; Oliveira, C.P.; Cogliati, B. Sorafenib reduces steatosis-induced fibrogenesis in a human 3D co-culture model of non-alcoholic fatty liver disease. Environ. Toxicol., 2021, 36(2), 168-176. doi: 10.1002/tox.23021 PMID: 32918399
  4. Zeng, Y.; He, H.; An, Z. Advance of serum biomarkers and combined diagnostic panels in nonalcoholic fatty liver disease. Dis. Markers, 2022, 2022, 1-12. doi: 10.1155/2022/1254014 PMID: 35811662
  5. Sahebkar, A.; Sancho, E.; Abelló, D.; Camps, J.; Joven, J. Novel circulating biomarkers for non-alcoholic fatty liver disease: A systematic review. J. Cell. Physiol., 2018, 233(2), 849-855. doi: 10.1002/jcp.25779 PMID: 28063221
  6. De Vincentis, A.; Rahmani, Z.; Muley, M.; Vespasiani- Gentilucci, U.; Ruggiero, S.; Zamani, P.; Jamialahmadi, T.; Sahebkar, A. Long noncoding RNAs in nonalcoholic fatty liver disease and liver fibrosis: state-of-the-art and perspectives in diagnosis and treatment. Drug Discov. Today, 2020, 25(7), 1277-1286. doi: 10.1016/j.drudis.2020.05.009 PMID: 32439605
  7. Mahmoudi, A.; Butler, A.E.; Jamialahmadi, T.; Sahebkar, A. The role of exosomal miRNA in nonalcoholic fatty liver disease. J. Cell. Physiol., 2022, 237(4), 2078-2094. doi: 10.1002/jcp.30699 PMID: 35137416
  8. Mahjoubin-Tehran, M.; De Vincentis, A.; Mikhailidis, D.P.; Atkin, S.L.; Mantzoros, C.S.; Jamialahmadi, T.; Sahebkar, A. Non-alcoholic fatty liver disease and steatohepatitis: State of the art on effective therapeutics based on the gold standard method for diagnosis. Mol. Metab., 2021, 50, 101049. doi: 10.1016/j.molmet.2020.101049 PMID: 32673798
  9. Ranjbar, G.; Mikhailidis, D.P.; Sahebkar, A. Effects of newer antidiabetic drugs on nonalcoholic fatty liver and steatohepatitis: Think out of the box! Metabolism, 2019, 101, 154001. doi: 10.1016/j.metabol.2019.154001 PMID: 31672448
  10. Mahmoudi, A.; Jamialahmadi, T.; Johnston, T.P.; Sahebkar, A. Impact of fenofibrate on NAFLD/NASH: A genetic perspective. Drug Discov. Today, 2022, 27(8), 2363-2372. doi: 10.1016/j.drudis.2022.05.007 PMID: 35569762
  11. Moosavian, S.A.; Sathyapalan, T.; Jamialahmadi, T.; Sahebkar, A. The emerging role of nanomedicine in the management of nonalcoholic fatty liver disease: A state-of-the-art review. Bioinorg. Chem. Appl., 2021, 2021, 1-13. doi: 10.1155/2021/4041415 PMID: 34659388
  12. Xu, X.; Poulsen, K.L.; Wu, L.; Liu, S.; Miyata, T.; Song, Q.; Wei, Q.; Zhao, C.; Lin, C.; Yang, J. Targeted therapeutics and novel signaling pathways in non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH). Signal Transduct. Target. Ther., 2022, 7(1), 287. doi: 10.1038/s41392-022-01119-3 PMID: 35963848
  13. Mantovani, A.; Dalbeni, A. Treatments for NAFLD: State of Art. Int. J. Mol. Sci., 2021, 26(22), 2350.
  14. Wei, T.; Hao, W.; Tang, L.; Wu, H.; Huang, S.; Yang, Y.; Qian, N.; Liu, J.; Yang, W.; Duan, X. Comprehensive RNA-Seq analysis of potential therapeutic targets of Gan– dou–fu–mu decoction for treatment of wilson disease using a toxic milk mouse model. Front. Pharmacol., 2021, 12, 622268. doi: 10.3389/fphar.2021.622268 PMID: 33935715
  15. Patel, K.; Sebastiani, G. Limitations of non-invasive tests for assessment of liver fibrosis. JHEP Reports, 2020, 2(2), 100067. doi: 10.1016/j.jhepr.2020.100067 PMID: 32118201
  16. Wong, V.W.S.; Adams, L.A.; de Lédinghen, V.; Wong, G.L.H.; Sookoian, S. Noninvasive biomarkers in NAFLD and NASH - current progress and future promise. Nat. Rev. Gastroenterol. Hepatol., 2018, 15(8), 461-478. doi: 10.1038/s41575-018-0014-9 PMID: 29844588
  17. Bolón-Canedo, V.; Alonso-Betanzos, A.; López-de-Ullibarri, I.; Cao, R. Challenges and future trends for microarray analysis. Methods Mol. Biol., 2019, 1986, 283-293. doi: 10.1007/978-1-4939-9442-7_14 PMID: 31115895
  18. Churko, J.M.; Mantalas, G.L.; Snyder, M.P.; Wu, J.C. Overview of high throughput sequencing technologies to elucidate molecular pathways in cardiovascular diseases. Circ. Res., 2013, 112(12), 1613-1623. doi: 10.1161/CIRCRESAHA.113.300939 PMID: 23743227
  19. Nishimura, A.; Matsumoto, N. Genomic microarray analysis of human diseases. Jpn. J. Clin. Med., 2010, 68(S8), 235-241. PMID: 20976902
  20. Wang, S.; Cheng, Q. Microarray analysis in drug discovery and clinical applications. Methods Mol. Biol., 2006, 316, 49-65. doi: 10.1385/1-59259-964-8:49 PMID: 16671400
  21. Clough, E.; Barrett, T. The gene expression omnibus database. Methods Mol. Biol., 2016, 1418, 93-110. doi: 10.1007/978-1-4939-3578-9_5 PMID: 27008011
  22. Athanasios, A.; Charalampos, V.; Vasileios, T.; Ashraf, G. Protein-protein interaction (PPI) network: Recent advances in drug discovery. Curr. Drug Metab., 2017, 18(1), 5-10. doi: 10.2174/138920021801170119204832 PMID: 28889796
  23. Mahmoudi, A.; Butler, A.E.; Majeed, M.; Banach, M.; Sahebkar, A. Investigation of the effect of curcumin on protein targets in nafld using bioinformatic analysis. Nutrients, 2022, 14(7), 1331. doi: 10.3390/nu14071331 PMID: 35405942
  24. Mahmoudi, A.; Heydari, S.; Markina, Y.V.; Barreto, G.E.; Sahebkar, A. Role of statins in regulating molecular pathways following traumatic brain injury: A system pharmacology study. Biomed. Pharmacother., 2022, 153, 113304. doi: 10.1016/j.biopha.2022.113304 PMID: 35724514
  25. Mahmoudi, A.; Butler, A.E.; Jamialahmadi, T.; Sahebkar, A. Target deconvolution of fenofibrate in nonalcoholic fatty liver disease using bioinformatics analysis. BioMed Res. Int., 2021, 2021, 1-14. doi: 10.1155/2021/3654660 PMID: 34988225
  26. Liu, J.; Lin, B.; Chen, Z.; Deng, M.; Wang, Y.; Wang, J.; Chen, L.; Zhang, Z.; Xiao, X.; Chen, C.; Song, Y. Identification of key pathways and genes in nonalcoholic fatty liver disease using bioinformatics analysis. Arch. Med. Sci., 2020, 16(2), 374-385. doi: 10.5114/aoms.2020.93343 PMID: 32190149
  27. Cotter, T.G.; Rinella, M. Nonalcoholic fatty liver disease 2020: The state of the disease. Gastroenterology, 2020, 158(7), 1851-1864. doi: 10.1053/j.gastro.2020.01.052 PMID: 32061595
  28. Byrne, C.D.; Targher, G. NAFLD: A multisystem disease. J. Hepatol., 2015, 62(S1), S47-S64. doi: 10.1016/j.jhep.2014.12.012 PMID: 25920090
  29. Liu, L.; Liu, C.; Zhao, M.; Zhang, Q.; Lu, Y.; Liu, P.; Yang, H.; Yang, J.; Chen, X.; Yao, Y. The pharmacodynamic and differential gene expression analysis of PPAR α/δ agonist GFT505 in CDAHFD-induced NASH model. PLoS One, 2020, 15(12), e0243911. doi: 10.1371/journal.pone.0243911 PMID: 33326461
  30. Ying, L.; Yan, F.; Zhao, Y.; Gao, H.; Williams, B.R.G.; Hu, Y.; Li, X.; Tian, R.; Xu, P.; Wang, Y. (-)-Epigallocatechin-3-gallate and atorvastatin treatment down-regulates liver fibrosis-related genes in non-alcoholic fatty liver disease. Clin. Exp. Pharmacol. Physiol., 2017, 44(12), 1180-1191. doi: 10.1111/1440-1681.12844 PMID: 28815679
  31. Asadipooya, K.; Lankarani, K.B.; Raj, R.; Kalantarhormozi, M. RAGE is a potential cause of onset and progression of nonalcoholic fatty liver disease. Int. J. Endocrinol., 2019, 2019, 1-11. doi: 10.1155/2019/2151302 PMID: 31641351
  32. Mahmoudi, A.; Atkin, S.L.; Nikiforov, N.G.; Sahebkar, A. Therapeutic role of curcumin in diabetes: An analysis based on bioinformatic findings. Nutrients, 2022, 14(15), 3244. doi: 10.3390/nu14153244 PMID: 35956419
  33. Hu, Q.; Wei, S.; Wen, J.; Zhang, W.; Jiang, Y.; Qu, C.; Xiang, J.; Zhao, Y.; Peng, X.; Ma, X. Network pharmacology reveals the multiple mechanisms of Xiaochaihu decoction in the treatment of non-alcoholic fatty liver disease. BioData Min., 2020, 13(1), 11. doi: 10.1186/s13040-020-00224-9 PMID: 32863886
  34. Zhang, M.; Yuan, Y.; Zhou, W.; Qin, Y.; Xu, K.; Men, J.; Lin, M. Network pharmacology analysis of Chaihu Lizhong Tang treating non-alcoholic fatty liver disease. Comput. Biol. Chem., 2020, 86, 107248. doi: 10.1016/j.compbiolchem.2020.107248 PMID: 32208163
  35. Polo, M.L.; Riggio, M.; May, M.; Rodríguez, M.J.; Perrone, M.C.; Stallings-Mann, M.; Kaen, D.; Frost, M.; Goetz, M.; Boughey, J.; Lanari, C.; Radisky, D.; Novaro, V. Activation of PI3K/Akt/mTOR signaling in the tumor stroma drives endocrine therapy-dependent breast tumor regression. Oncotarget, 2015, 6(26), 22081-22097. doi: 10.18632/oncotarget.4203 PMID: 26098779
  36. Xia, P.; Xu, X.Y. PI3K/Akt/mTOR signaling pathway in cancer stem cells: From basic research to clinical application. Am. J. Cancer Res., 2015, 5(5), 1602-1609. PMID: 26175931
  37. Ersahin, T.; Tuncbag, N.; Cetin-Atalay, R. The PI3K/AKT/mTOR interactive pathway. Mol. Biosyst., 2015, 11(7), 1946-1954. doi: 10.1039/C5MB00101C PMID: 25924008
  38. Wang, R.; Song, F.; Li, S.; Wu, B.; Gu, Y.; Yuan, Y. Salvianolic acid A attenuates CCl4-induced liver fibrosis by regulating the PI3K/AKT/mTOR, Bcl-2/Bax and caspase-3/cleaved caspase-3 signaling pathways. Drug Des. Devel. Ther., 2019, 13, 1889-1900. doi: 10.2147/DDDT.S194787 PMID: 31213776
  39. Ackers, I.; Malgor, R. Interrelationship of canonical and non-canonical Wnt signalling pathways in chronic metabolic diseases. Diab. Vasc. Dis. Res., 2018, 15(1), 3-13. doi: 10.1177/1479164117738442 PMID: 29113510
  40. Tian, Y.; Mok, M.; Yang, P.; Cheng, A. Epigenetic activation of Wnt/β-catenin signaling in NAFLD-associated hepatocarcinogenesis. Cancers, 2016, 8(8), 76. doi: 10.3390/cancers8080076 PMID: 27556491
  41. Wang, X-M.; Wang, X-Y.; Huang, Y-M.; Chen, X.; Lü, M-H.; Shi, L.; Li, C.P. Role and mechanisms of action of microRNA-21 as regards the regulation of the WNT/β- catenin signaling pathway in the pathogenesis of non-alcoholic fatty liver disease. Int. J. Mol. Med., 2019, 44(6), 2201-2212. doi: 10.3892/ijmm.2019.4375 PMID: 31638173
  42. Wang, S.; Song, K.; Srivastava, R.; Dong, C.; Go, G.W.; Li, N.; Iwakiri, Y.; Mani, A. Nonalcoholic fatty liver disease induced by noncanonical Wnt and its rescue by Wnt3a. FASEB J., 2015, 29(8), 3436-3445. doi: 10.1096/fj.15-271171 PMID: 25917329
  43. Luo, Z.Y.; Song, Q.; Xiong, X.P.; Abdulai, M.; Liu, H.H.; Li, L.; Xu, H.Y.; Hu, S.Q.; Han, C.C. The pi3k/akt/mtor signaling pathway regulates lipid metabolism mediated by endoplasmic reticulum stress in goose primary hepatocytes. Eur. Polit. Sci., 2021, 85, 1-15.
  44. Liu, B.; Deng, X.; Jiang, Q.; Li, G.; Zhang, J.; Zhang, N.; Xin, S.; Xu, K. Scoparone improves hepatic inflammation and autophagy in mice with nonalcoholic steatohepatitis by regulating the ROS/P38/Nrf2 axis and PI3K/AKT/mTOR pathway in macrophages. Biomed. Pharmacother., 2020, 125, 109895. doi: 10.1016/j.biopha.2020.109895 PMID: 32000066
  45. Fan, Y.; He, Z.; Wang, W.; Li, J.; Hu, A.; Li, L.; Yan, L.; Li, Z.; Yin, Q. Tangganjian decoction ameliorates type 2 diabetes mellitus and nonalcoholic fatty liver disease in rats by activating the IRS/PI3K/AKT signaling pathway. Biomed. Pharmacother., 2018, 106, 733-737. doi: 10.1016/j.biopha.2018.06.089 PMID: 29990865
  46. Hohwieler, M.; Perkhofer, L.; Liebau, S.; Seufferlein, T.; Müller, M.; Illing, A.; Kleger, A. Stem cell-derived organoids to model gastrointestinal facets of cystic fibrosis. United European Gastroenterol. J., 2017, 5(5), 609-624. doi: 10.1177/2050640616670565 PMID: 28815024
  47. Mallea, J.; Bolan, C.; Cortese, C.; Harnois, D. Cystic fibrosis–associated liver disease in lung transplant recipients. Liver Transpl., 2019, 25(8), 1265-1275. doi: 10.1002/lt.25496 PMID: 31102574
  48. Martin, C.R.; Zaman, M.M.; Ketwaroo, G.A.; Bhutta, A.Q.; Coronel, E.; Popov, Y.; Schuppan, D.; Freedman, S.D. CFTR dysfunction predisposes to fibrotic liver disease in a murine model. Am. J. Physiol. Gastrointest. Liver Physiol., 2012, 303(4), G474-G481. doi: 10.1152/ajpgi.00055.2012 PMID: 22679000
  49. Ricard-Blum, S. The collagen family. Cold Spring Harb. Perspect. Biol., 2011, 3(1), a004978. doi: 10.1101/cshperspect.a004978 PMID: 21421911
  50. Escutia-Gutiérrez, R.; Rodríguez-Sanabria, J.S.; Monraz-Méndez, C.A.; García-Bañuelos, J.; Santos-García, A.; Sandoval-Rodríguez, A.; Armendáriz-Borunda, J. Pirfenidone modifies hepatic miRNAs expression in a model of MAFLD/NASH. Sci. Rep., 2021, 11(1), 11709. doi: 10.1038/s41598-021-91187-2 PMID: 34083664
  51. Sámano-Hernández, L.; Fierro, R.; Marchal, A.; Guéant, J.L.; González-Márquez, H.; Guéant-Rodríguez, R.M. Beneficial and deleterious effects of sitagliptin on a methionine/choline-deficient diet-induced steatohepatitis in rats. Biochimie, 2021, 181, 240-248. doi: 10.1016/j.biochi.2020.12.004 PMID: 33333172
  52. Fan, Y.; Fang, X.; Tajima, A.; Geng, X.; Ranganathan, S.; Dong, H.; Trucco, M.; Sperling, M.A. Evolution of hepatic steatosis to fibrosis and adenoma formation in liver-specific growth hormone receptor knockout mice. Front. Endocrinol., 2014, 5, 218. doi: 10.3389/fendo.2014.00218 PMID: 25566190
  53. Islam, S.; Watanabe, H. Versican: A dynamic regulator of the extracellular matrix. J. Histochem. Cytochem., 2020, 68(11), 763-775. doi: 10.1369/0022155420953922 PMID: 33131383
  54. Bukong, T.N.; Maurice, S.B.; Chahal, B.; Schaeffer, D.F.; Winwood, P.J. Versican: A novel modulator of hepatic fibrosis. Lab. Invest., 2016, 96(3), 361-374. doi: 10.1038/labinvest.2015.152 PMID: 26752747
  55. Wight, T.N.; Kang, I.; Merrilees, M.J. Versican and the control of inflammation. Matrix Biol., 2014, 35, 152-161. doi: 10.1016/j.matbio.2014.01.015 PMID: 24513039
  56. Kim, S.; Takahashi, H.; Lin, W.W.; Descargues, P.; Grivennikov, S.; Kim, Y.; Luo, J.L.; Karin, M. Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis. Nature, 2009, 457(7225), 102-106. doi: 10.1038/nature07623 PMID: 19122641
  57. Kesteloot, F.; Desmoulière, A.; Leclercq, I.; Thiry, M.; Arrese, J.E.; Prockop, D.J.; Lapière, C.M.; Nusgens, B.V.; Colige, A. ADAM metallopeptidase with thrombospondin type 1 motif 2 inactivation reduces the extent and stability of carbon tetrachloride-induced hepatic fibrosis in mice. Hepatology, 2007, 46(5), 1620-1631. doi: 10.1002/hep.21868 PMID: 17929299
  58. Bauters, D.; Spincemaille, P.; Geys, L.; Cassiman, D.; Vermeersch, P.; Bedossa, P.; Scroyen, I.; Lijnen, H.R. ADAMTS5 deficiency protects against non-alcoholic steatohepatitis in obesity. Liver Int., 2016, 36(12), 1848-1859. doi: 10.1111/liv.13181 PMID: 27254774
  59. Ramnath, D.; Irvine, K.M.; Lukowski, S.W.; Horsfall, L.U.; Loh, Z.; Clouston, A.D.; Patel, P.J.; Fagan, K.J.; Iyer, A.; Lampe, G.; Stow, J.L.; Schroder, K.; Fairlie, D.P.; Powell, J.E.; Powell, E.E.; Sweet, M.J. Hepatic expression profiling identifies steatosis-independent and steatosis-driven advanced fibrosis genes. JCI Insight, 2018, 3(14), e120274. doi: 10.1172/jci.insight.120274 PMID: 30046009
  60. Sadler, J.E. Biochemistry and genetics of von Willebrand factor. Annu. Rev. Biochem., 1998, 67(1), 395-424. doi: 10.1146/annurev.biochem.67.1.395 PMID: 9759493
  61. Groeneveld, D.J.; Poole, L.G.; Luyendyk, J.P. Targeting von Willebrand factor in liver diseases: A novel therapeutic strategy? J. Thromb. Haemost., 2021, 19(6), 1390-1408. doi: 10.1111/jth.15312 PMID: 33774926
  62. Rosito, G.; D’Agostino, R.; Massaro, J.; Lipinska, I.; Mittleman, M.; Sutherland, P.; Wilson, P.; Levy, D.; Muller, J.; Tofler, G. Association between obesity and a prothrombotic state: The Framingham Offspring Study. Thromb. Haemost., 2004, 91(4), 683-689. doi: 10.1160/TH03-01-0014 PMID: 15045128
  63. Bilgir, O.; Bilgir, F.; Bozkaya, G.; Calan, M. Changes in the levels of endothelium-derived coagulation parameters in nonalcoholic fatty liver disease. Blood Coagul. Fibrinolysis, 2014, 25(2), 151-155. doi: 10.1097/MBC.0000000000000009 PMID: 24317388
  64. Danoy, M.; Jellali, R.; Tauran, Y.; Bruce, J.; Leduc, M.; Gilard, F.; Gakière, B.; Scheidecker, B.; Kido, T.; Miyajima, A.; Soncin, F.; Sakai, Y.; Leclerc, E. Characterization of the proteome and metabolome of human liver sinusoidal endothelial-like cells derived from induced pluripotent stem cells. Differentiation, 2021, 120, 28-35. doi: 10.1016/j.diff.2021.06.001 PMID: 34229994
  65. Yang, J.; Lu, Y.; Lou, X.; Wang, J.; Yu, H.; Bao, Z.; Wang, H. Von willebrand factor deficiency improves hepatic steatosis, insulin resistance, and inflammation in mice fed high-fat diet. Obesity, 2020, 28(4), 756-764. doi: 10.1002/oby.22744 PMID: 32144880
  66. Menggensilimu; Yuan, H.; Zhao, C.; Bao, X.; Wang, H.; Liang, J.; Yan, Y.; Zhang, C.; Jin, R.; Ma, L.; Zhang, J.; Su, X.; Ma, Y. Anti-liver fibrosis effect of total flavonoids from Scabiosa comosa Fisch. ex Roem. et Schult. on liver fibrosis in rat models and its proteomics analysis. Ann. Palliat. Med., 2020, 9(2), 272-285. doi: 10.21037/apm.2020.02.29 PMID: 32233617
  67. Fisher, L.W.; Torchia, D.A.; Fohr, B.; Young, M.F.; Fedarko, N.S. Flexible structures of SIBLING proteins, bone sialoprotein, and osteopontin. Biochem. Biophys. Res. Commun., 2001, 280(2), 460-465. doi: 10.1006/bbrc.2000.4146 PMID: 11162539
  68. Sahai, A.; Malladi, P.; Melin-Aldana, H.; Green, R.M.; Whitington, P.F. Upregulation of osteopontin expression is involved in the development of nonalcoholic steatohepatitis in a dietary murine model. Am. J. Physiol. Gastrointest. Liver Physiol., 2004, 287(1), G264-G273. doi: 10.1152/ajpgi.00002.2004 PMID: 15044174
  69. Banerjee, A.; Rose, R.; Johnson, G.A.; Burghardt, R.C.; Ramaiah, S.K. The influence of estrogen on hepatobiliary osteopontin (SPP1) expression in a female rodent model of alcoholic steatohepatitis. Toxicol. Pathol., 2009, 37(4), 492-501. doi: 10.1177/0192623309335633 PMID: 19387089
  70. Sweetwyne, M.T.; Murphy-Ullrich, J.E. Thrombospondin1 in tissue repair and fibrosis: TGF-β-dependent and independent mechanisms. Matrix Biol., 2012, 31(3), 178-186. doi: 10.1016/j.matbio.2012.01.006 PMID: 22266026
  71. Adams, J.C.; Lawler, J. The Thrombospondins. Cold Spring Harb. Perspect. Biol., 2011, 3(10), a009712. doi: 10.1101/cshperspect.a009712 PMID: 21875984
  72. Maimaitiyiming, H.; Clemons, K.; Zhou, Q.; Norman, H.; Wang, S. Thrombospondin1 deficiency attenuates obesity-associated microvascular complications in ApoE-/- mice. PLoS One, 2015, 10(3), e0121403. doi: 10.1371/journal.pone.0121403 PMID: 25803585
  73. Wang, S.; Lincoln, T.M.; Murphy-Ullrich, J.E. Glucose downregulation of PKG-I protein mediates increased thrombospondin1-dependent TGF-β activity in vascular smooth muscle cells. Am. J. Physiol. Cell Physiol., 2010, 298(5), C1188-C1197. doi: 10.1152/ajpcell.00330.2009 PMID: 20164378
  74. Lopez-Dee, Z.; Pidcock, K.; Gutierrez, L.S. Thrombospondin-1: Multiple paths to inflammation. Mediators Inflamm., 2011, 2011, 1-10. doi: 10.1155/2011/296069 PMID: 21765615
  75. Li, Y.; Turpin, C.P.; Wang, S. Role of thrombospondin 1 in liver diseases. Hepatol. Res., 2017, 47(2), 186-193. doi: 10.1111/hepr.12787 PMID: 27492250
  76. Min-DeBartolo, J.; Schlerman, F.; Akare, S.; Wang, J.; McMahon, J.; Zhan, Y.; Syed, J.; He, W.; Zhang, B.; Martinez, R.V. Thrombospondin-I is a critical modulator in non-alcoholic steatohepatitis (NASH). PLoS One, 2019, 14(12), e0226854. doi: 10.1371/journal.pone.0226854 PMID: 31891606
  77. Li, Y.; Qi, X.; Tong, X.; Wang, S. Thrombospondin 1 activates the macrophage Toll-like receptor 4 pathway. Cell. Mol. Immunol., 2013, 10(6), 506-512. doi: 10.1038/cmi.2013.32 PMID: 23954950
  78. Gwag, T.; Reddy Mooli, R.G.; Li, D.; Lee, S.; Lee, E.Y.; Wang, S. Macrophage-derived thrombospondin 1 promotes obesity-associated non-alcoholic fatty liver disease. JHEP Reports, 2021, 3(1), 100193. doi: 10.1016/j.jhepr.2020.100193 PMID: 33294831
  79. Song, Y.; Gao, L. Thrombospondin1 as a potential therapeutic target for human nonalcoholic fatty liver disease. EBioMedicine, 2020, 58, 102888. doi: 10.1016/j.ebiom.2020.102888 PMID: 32697967
  80. Kimura, T.; Tanaka, N.; Fujimori, N.; Yamazaki, T.; Katsuyama, T.; Iwashita, Y.; Pham, J.; Joshita, S.; Pydi, S.P.; Umemura, T. Serum thrombospondin 2 is a novel predictor for the severity in the patients with NAFLD. Liver Int., 2021, 41(3), 505-514. doi: 10.1111/liv.14776 PMID: 33386676
  81. Wolff, G.; Taranko, A.E.; Meln, I.; Weinmann, J.; Sijmonsma, T.; Lerch, S.; Heide, D.; Billeter, A.T.; Tews, D.; Krunic, D.; Fischer-Posovszky, P.; Müller-Stich, B.P.; Herzig, S.; Grimm, D.; Heikenwälder, M.; Kao, W.W.; Vegiopoulos, A. Diet-dependent function of the extracellular matrix proteoglycan Lumican in obesity and glucose homeostasis. Mol. Metab., 2019, 19, 97-106. doi: 10.1016/j.molmet.2018.10.007 PMID: 30409703
  82. Charlton, M.; Viker, K.; Krishnan, A.; Sanderson, S.; Veldt, B.; Kaalsbeek, A.J.; Kendrick, M.; Thompson, G.; Que, F.; Swain, J.; Sarr, M. Differential expression of lumican and fatty acid binding protein-1: New insights into the histologic spectrum of nonalcoholic fatty liver disease. Hepatology, 2009, 49(4), 1375-1384. doi: 10.1002/hep.22927 PMID: 19330863
  83. Krishnan, A.; Li, X.; Kao, W.Y.; Viker, K.; Butters, K.; Masuoka, H.; Knudsen, B.; Gores, G.; Charlton, M. Lumican, an extracellular matrix proteoglycan, is a novel requisite for hepatic fibrosis. Lab. Invest., 2012, 92(12), 1712-1725. doi: 10.1038/labinvest.2012.121 PMID: 23007134
  84. Decaris, M.L.; Li, K.W.; Emson, C.L.; Gatmaitan, M.; Liu, S.; Wang, Y.; Nyangau, E.; Colangelo, M.; Angel, T.E.; Beysen, C.; Cui, J.; Hernandez, C.; Lazaro, L.; Brenner, D.A.; Turner, S.M.; Hellerstein, M.K.; Loomba, R. Identifying nonalcoholic fatty liver disease patients with active fibrosis by measuring extracellular matrix remodeling rates in tissue and blood. Hepatology, 2017, 65(1), 78-88. doi: 10.1002/hep.28860 PMID: 27706836
  85. Chang, Y.; He, J.; Xiang, X.; Li, H. LUM is the hub gene of advanced fibrosis in nonalcoholic fatty liver disease patients. Clin. Res. Hepatol. Gastroenterol., 2021, 45(1), 101435. doi: 10.1016/j.clinre.2020.04.006 PMID: 32386798
  86. Karamfilova, V.; Gateva, A.; Assyov, Y.; Nedeva, I.; Velikova, T.; Cherkezov, N.; Mateva, L.; Kamenov, Z. Lumican in obese patients with nonalcoholic fatty liver disease with or without prediabetes. Metab. Syndr. Relat. Disord., 2020, 18(9), 443-448. doi: 10.1089/met.2020.0001 PMID: 32780624
  87. Ciupińska-Kajor, M.; Hartleb, M.; Kajor, M.; Kukla, M.; Wyleżoł, M.; Lange, D.; Liszka, Ł. Hepatic angiogenesis and fibrosis are common features in morbidly obese patients. Hepatol. Int., 2013, 7(1), 233-240. doi: 10.1007/s12072-011-9320-9 PMID: 23519653
  88. Suzawa, K.; Kobayashi, M.; Sakai, Y.; Hoshino, H.; Watanabe, M.; Harada, O.; Ohtani, H.; Fukuda, M.; Nakayama, J. Preferential induction of peripheral lymph node addressin on high endothelial venule-like vessels in the active phase of ulcerative colitis. Am. J. Gastroenterol., 2007, 102(7), 1499-1509. doi: 10.1111/j.1572-0241.2007.01189.x PMID: 17459027
  89. Strilić, B.; Kučera, T.; Eglinger, J.; Hughes, M.R.; McNagny, K.M.; Tsukita, S.; Dejana, E.; Ferrara, N.; Lammert, E. The molecular basis of vascular lumen formation in the developing mouse aorta. Dev. Cell, 2009, 17(4), 505-515. doi: 10.1016/j.devcel.2009.08.011 PMID: 19853564
  90. Shi, J.F.; Xu, S.X.; He, P.; Xi, Z.H. Expression of carcinoembryonic antigen-related cell adhesion molecule 1(CEACAM1) and its correlation with angiogenesis in gastric cancer. Pathol. Res. Pract., 2014, 210(8), 473-476. doi: 10.1016/j.prp.2014.03.014 PMID: 24846314
  91. Kukla, M.; Gabriel, A.; Sabat, D.; Liszka, Ł.; Wilk, M.; Petelenz, M.; Musialik, J.; Dzindziora-Frelich, I. Association between liver steatosis and angiogenesis in chronic hepatitis C. Pol. J. Pathol., 2010, 61(3), 154-160. PMID: 21225498
  92. Tsuji, N.; Ishiguro, S.; Sasaki, Y.; Kudo, M. CD34 expression in noncancerous liver tissue predicts multicentric recurrence of hepatocellular carcinoma. Dig. Dis., 2013, 31(5-6), 467-471. doi: 10.1159/000355246 PMID: 24281022
  93. Cui, D.J.; Wu, Y.; Wen, D.H. CD34, PCNA and CK19 expressions in AFP-hepatocellular carcinoma. Eur. Rev. Med. Pharmacol. Sci., 2018, 22(16), 5200-5205. PMID: 30178842
  94. Yan, W.W.; Huang, A.; Li, Y.G.; Wang, S.S.; Dai, G.H. Expressions of CD34 and CD117 in human hepatocellular carcinomas and the clinical significance. Zhonghua Gan Zang Bing Za Zhi, 2011, 19(8), 588-593. PMID: 22152315
  95. Zhang, Q.; Chen, X.; Zhou, J.; Zhang, L.; Zhao, Q.; Chen, G.; Xu, J.; Feng, Q.; Chen, Z. CD147, MMP-2, MMP-9 and MVD-CD34 are significant predictors of recurrence after liver transplantation in hepatocellular carcinoma patients. Cancer Biol. Ther., 2006, 5(7), 808-814. doi: 10.4161/cbt.5.7.2754 PMID: 16775432
  96. Choi, W.T.; Kakar, S. Immunohistochemistry in the diagnosis of hepatocellular carcinoma. Gastroenterol. Clin. North Am., 2017, 46(2), 311-325. doi: 10.1016/j.gtc.2017.01.006 PMID: 28506367
  97. Li, Y.; Song, D.; Mao, L.; Abraham, D.M.; Bursac, N. Lack of Thy1 defines a pathogenic fraction of cardiac fibroblasts in heart failure. Biomaterials, 2020, 236, 119824. doi: 10.1016/j.biomaterials.2020.119824 PMID: 32028169
  98. Dudas, J.; Mansuroglu, T.; Batusic, D.; Saile, B.; Ramadori, G. Thy-1 is an in vivo and in vitro marker of liver myofibroblasts. Cell Tissue Res., 2007, 329(3), 503-514. doi: 10.1007/s00441-007-0437-z PMID: 17576600
  99. Kon, J.; Ichinohe, N.; Ooe, H.; Chen, Q.; Sasaki, K.; Mitaka, T. Thy1-positive cells have bipotential ability to differentiate into hepatocytes and biliary epithelial cells in galactosamine-induced rat liver regeneration. Am. J. Pathol., 2009, 175(6), 2362-2371. doi: 10.2353/ajpath.2009.080338 PMID: 19893024
  100. Zheng, J.; Wu, H.; Zhang, Z.; Yao, S. Dynamic co-expression modular network analysis in nonalcoholic fatty liver disease. Hereditas, 2021, 158(1), 31. doi: 10.1186/s41065-021-00196-8 PMID: 34419146
  101. Pepper, S.D.; Saunders, E.K.; Edwards, L.E.; Wilson, C.L.; Miller, C.J. The utility of MAS5 expression summary and detection call algorithms. BMC Bioinformatics, 2007, 8(1), 273. doi: 10.1186/1471-2105-8-273 PMID: 17663764
  102. Shannon, P.; Markiel, A.; Ozier, O.; Baliga, N.S.; Wang, J.T.; Ramage, D.; Amin, N.; Schwikowski, B.; Ideker, T. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res., 2003, 13(11), 2498-2504. doi: 10.1101/gr.1239303 PMID: 14597658
  103. Jacomy, M.; Venturini, T.; Heymann, S.; Bastian, M. ForceAtlas2, a continuous graph layout algorithm for handy network visualization designed for the Gephi software. PLoS One, 2014, 9(6), e98679. doi: 10.1371/journal.pone.0098679 PMID: 24914678

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