REFERENCES
  1. Rockey DC, Bell PD, Hill JA. Fibrosis-a common pathway to organ injury and failure. N Engl J Med 2015;372:1138-1149.
  2. Bataller R, Brenner DA. Liver fibrosis. J Clin Invest 2005;115:209-218.
  3. Blachier M, Leleu H, Peck-Radosavljevic M, Valla DC, Roudot-Thoraval F. The burden of liver disease in Europe: A review of available epidemiological data. J Hepatol 2013;58:593-608.
  4. Mederacke I, Hsu CC, Troeger JS, Huebener P, Mu X, Dapito DH, et al. Fate tracing reveals hepatic stellate cells as dominant contributors to liver fibrosis independent of its aetiology. Nat Commun 2013;4:2823.
  5. Iwaisako K, Jiang C, Zhang M, Cong M, Moore-Morris TJ, Park TJ, et al. Origin of myofibroblasts in the fibrotic liver in mice. Proc Natl Acad Sci USA 2014;111:E3297-E3305.
  6. Kisseleva T. The origin of fibrogenic myofibroblasts in fibrotic liver. Hepatology 2017;65:1039-1043.
  7. de Lecea L, Criado JR, Prospero-Garcia O, Gautvik KM, Schweitzer P, Danielson PE, et al. A cortical neuropeptide with neuronal depressant and sleep-modulating properties. Nature 1996;381:242-245.
  8. Gonzalez-Rey E, Delgado M. Emergence of cortistatin as a new immunomodulatory factor with therapeutic potential in immune disorders. Mol Cell Endocrinol 2008;286:135-40.
  9. Gonzalez-Rey E, Chorny A, Robledo G, Delgado M. Cortistatin, a new antiinflammatory peptide with therapeutic effect on lethal endotoxemia. J Exp Med 2006;203:563-571.
  10. Delgado-Maroto V, Falo CP, Forte-Lago I, Adan N, Morell M, Maganto-Garcia E, et al. The neuropeptide cortistatin attenuates experimental autoimmune myocarditis via inhibition of cardiomyogenic T cell-driven inflammatory responses. Br J Pharmacol 2017;174:267-280.
  11. Gonzalez-Rey E, Chorny A, Del Moral RG, Varela N, Delgado M. Therapeutic effect of cortistatin on experimental arthritis by downregulating inflammatory and Th1 responses. Ann Rheum Dis 2007;66:582-588.
  12. Gonzalez-Rey E, Varela N, Sheibanie AF, Chorny A, Ganea D, Delgado M. Cortistatin, an antiinflammatory peptide with therapeutic action in inflammatory bowel disease. Proc Natl Acad Sci USA 2006;103:4228-4233.
  13. Tracy TF, Tector AJ, Goerke ME, Kitchen S, Lagunoff D. Somatostatin analogue (Octreotide) inhibits bile duct epithelial cell proliferation and fibrosis after extrahepatic biliary obstruction. Am J Pathol 1993;143:1574-1578.
  14. Moreno M, Chaves JF, Sancho-Bru P, Ramalho F, Ramalho LN, Mansego ML, et al. Ghrelin attenuates hepatocellular injury and liver fibrogenesis in rodents and influences fibrosis progression in humans. Hepatology 2010;51:974-985.
  15. Sikiric P, Seiwerth S, Grabarevic Z, Rucman R, Petek M, Rotkvic I, et al. Hepatoprotective effect of BPC 157, a 15-amino acid peptide, on liver lesions induced by either restraint stress or bile duct and hepatic artery ligation or CCl4 administration. A comparative study with dopamine agonists and somatostatin. Life Sci 1993;53:PL291-PL296.
  16. Reynaert H, Vaeyens F, Qin H, Hellemans K, Chatterjee N, Winand D, et al. Somatostatin suppresses endothelin-1-induced rat hepatic stellate cell contraction via somatostatin receptor subtype 1. Gastroenterology 2001;121:915-930.
  17. Fort J, Oberti F, Pilette C, Veal N, Gallois Y, Douay O, et al. Antifibrotic and hemodynamic effects of the early and chronic administration of octreotide in two models of liver fibrosis in rats. Hepatology 1998;28:1525-1531.
  18. Reynaert H, Rombouts K, Vandermonde A, Urbain D, Kumar U, Bioulac-Sage P, et al. Expression of somatostatin receptors in normal and cirrhotic human liver and in hepatocellular carcinoma. Gut 2004;53:1180-1189.
  19. Reynaert H, Rombouts K, Jia Y, Urbain D, Chatterjee N, Uyama N, et al. Somatostatin at nanomolar concentration reduces collagen I and III synthesis by, but not proliferation of activated rat hepatic stellate cells. Br J Pharmacol 2005;146:77-88.
  20. Borie R, Fabre A, Prost F, Marchal-Somme J, Lebtahi R, Marchand-Adam S, et al. Activation of somatostatin receptors attenuates pulmonary fibrosis. Thorax 2008;63:251-258.
  21. Duran-Prado M, Morell M, Delgado-Maroto V, Castaño JP, Aneiros-Fernandez J, De Lecea L, et al. Cortistatin inhibits migration and proliferation of human vascular smooth muscle cells and decreases neointimal formation on carotid artery ligation. Circ Res 2013;112:1444-1455.
  22. Morell M, Camprubí-Robles M, Culler MD, de Lecea L, Delgado M. Cortistatin attenuates inflammatory pain via spinal and peripheral actions. Neurobiol Dis 2014;63:141-154.
  23. Liu Y, Lin F, Fu Y, Chen W, Liu W, Chi J, et al. Cortistatin inhibits arterial calcification in rats via GSK3β/β-catenin and protein kinase C signalling but not c-Jun N-terminal kinase signalling. Acta Physiol (Oxf) 2018;223:e13055.
  24. Wang M, Gong Q, Zhang J, Chen L, Zhang Z, Lu L, et al. Characterization of gene expression profiles in HBV-related liver fibrosis patients and identification of ITGBL1 as a key regulator of fibrogenesis. Sci Rep 2017;7:43446.
  25. Mas VR, Maluf DG, Archer KJ, Yanek K, Kong X, Kulik L, et al. Genes involved in viral carcinogenesis and tumor initiation in hepatitis C virus-induced hepatocellular carcinoma. Mol Med 2009;15:85-94.
  26. Moylan CA, Pang H, Dellinger A, Suzuki A, Garrett ME, Guy CD, et al. Hepatic gene expression profiles differentiate presymptomatic patients with mild versus severe nonalcoholic fatty liver disease. Hepatology 2014;59:471-482.
  27. Percie du Sert N, Hurst V, Ahluwalia A, Alam S, Avey MT, Baker Met al . The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. Br J Pharmacol 2020;177:3617-3624.
  28. Córdoba-Chacón J, Gahete MD, Pozo-Salas AI, Martinez-Fuentes AJ, De Lecea L, Gracia-Navarro F, et al. Cortistatin is not a somatostatin analogue but stimulates prolactin release and inhibits GH and ACTH in a gender-dependent fashion: potential role of ghrelin. Endocrinology 2011;152:4800-4812.
  29. Seki E, De Minicis S, Österreicher CH, Kluwe J, Osawa Y, Brenner DA, et al. TLR4 enhances TGF-beta signaling and hepatic fibrosis. Nat Med 2007;13:1324-1332.
  30. Reddy GK, Enwemeka CS. A simplified method for the analysis of hydroxyproline in biological tissues. Clin Biochem 1996;29:225-229.
  31. Weiskirchen S, Tag CG, Sauer-Lehnen S, Tacke F, Weiskirchen R. Isolation and culture of primary murine hepatic stellate cells. Methods Mol Biol 2017;1627:165-191.
  32. Gautier L, Cope L, Bolstad BM, Irizarry RA. “affy—analysis of Affymetrix GeneChip data at the probe level.” Bioinformatics 2004;20:307-315.
  33. Ishak KG. Chronic hepatitis: morphology and nomenclature. Mod Pathol 1994;7:690-713.
  34. Standish RA, Cholongitas E, Dhillon A, Burroughs AK, Dhillon AP. An appraisal of the histopathological assessment of liver fibrosis. Gut 2006;55:569-578.
  35. Andres-Leon E, Nunez-Torres R, Rojas AM. miARma-Seq: a comprehensive tool for miRNA, mRNA and circRNA analysis. Sci Rep 2016;6:25749.
  36. Nikolayeva O, Robinson MD. edgeR for differential RNA-seq and ChIP-seq analysis: an application to stem cell biology. Methods Mol Biol 2014;1150:45-79.
  37. Robinson MD, Oshlack A. A scaling normalization method for differential expression analysis of RNA-seq data. Genome Biol 2010;11:R25
  38. Reeb PD, Bramardi SJ, Steibel JP. Assessing dissimilarity measures for sample-based Hierarchical Clustering of RNA sequencing data using Plasmode Datasets. PLoS One 2015;10:e0132310.
  39. Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, et al. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res 2015;43:e47.
  40. Yu G, Wang L-G, Han Y, He QY. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS 2012;16:284.
  41. Curtis MJ, Alexander S, Cirino G, Docherty JR, George CH, Giembycz MAet al. Experimental design and analysis and their reporting II: updated and simplified guidance for authors and peer reviewers. Br J Pharmacol 2018;175:987-993.
  42. Xu L, Huy AY, Albanis E, Arthur MJ, O’Byrne SM, Blaner WS, et al. Human hepatic stellate cell lines, LX-1 and LX-2: new tools for analysis of hepatic fibrosis. Gut 2005; 54:142-151.
  43. Hernandez-Gea V, Friedman SL. Pathogenesis of liver fibrosis. Annu Rev Pathol 2011;6:425-456.
  44. Hagashi T, Friedman SL, Hoshida Y. Hepatic stellate cells as key target in liver fibrosis. Adv Drug Deliv Rev 2017;121:27-42.
  45. De Minicis S, Seki E, Uchinami H, Kluwe J, Zhang Y, Brenner DA, et al. Gene expression profiles during hepatic stellate cell activation in culture and in vivo. Gastroenterology 2007;132:1937-1946.
  46. Tsuchida T, Friedman SL. Mechanisms of hepatic stellate cell activation. Nat Rev Gastroenterol Hepatol 2017;14:397-411.
  47. Troeger JS, Mederacke I, Gwak G-Y, Dapito DH, Mu X, Hsu CC, et al. Deactivation of hepatic stellate cells during liver fibrosis resolution in mice. Gastroenterology 2012;143:1073-1083.
  48. Kisseleva T, Cong M, Paik Y, Scholten D, Jiang C, Benner C, et al. Myofibroblasts revert to an inactive phenotype during regression of liver fibrosis. Proc Natl Acad Sci USA 2012;109:9448-9453.
  49. Kisseleva T, Brenner D. Molecular and cellular mechanisms of liver fibrosis and its regression. Nat Rev Gastroenterol Hepatol 2021;18:151-166.
  50. Ibañez-Costa A, Luque RM, Castaño JP. Cortistatin: a new link between the growth hormone/prolactin axis, stress and metabolism. Growth Horm IGF Res 2017;33:23-27.
  51. Jordan VK, Zaveri HP, Scott DA. 1p36 deletion syndrome: An update. Appl Clin Genet 2015;8:189-200.
  52. Giordano R, Picu A, Bonelli L, Broglio F, Prodam F, Grottoli S, et al. The activation of somatostatinergic receptors by either somatostatin-14 or cortistatin-17 often inhibits ACTH hypersecretion in patients with Cushing’s disease. Eur J Endocrinol 2007;157:393-398.
  53. Rol A, Todorovski T, Martin-Malpartida P, Escola A, Gonzalez-Rey E, Aragon E, et al. Structure-based design of a cortistatin analogue with immunoregulatory activity in models of inflammatory bowel disease. Nat Commun 2021;12:1869.