Human Hepatocellular Response in Cholestatic Liver Diseases

Overview

Journal Organogenesis

Specialties Anatomy & Histology
Biology
Biotechnology

Date 2023 Aug 20

PMID 37598346

Authors

Kimberly Ortiz

Zeliha Cetin

Yiyue Sun

Zhiping Hu

Takeshi Kurihara

Edgar N Tafaleng

Rodrigo M Florentino

Alina Ostrowska

Alejandro Soto-Gutierrez

Lanuza A P Faccioli

Affiliations

Soon will be listed here.

Abstract

Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), the most common types of cholestatic liver disease (CLD), result in enterohepatic obstruction, bile acid accumulation, and hepatotoxicity. The mechanisms by which hepatocytes respond to and cope with CLD remain largely unexplored. This study includes the characterization of hepatocytes isolated from explanted livers of patients with PBC and PSC. We examined the expression of hepatocyte-specific genes, intracellular bile acid (BA) levels, and oxidative stress in primary-human-hepatocytes (PHHs) isolated from explanted livers of patients with PBC and PSC and compared them with control normal human hepatocytes. Our findings provide valuable initial insights into the hepatocellular response to cholestasis in CLD and help support the use of PHHs as an experimental tool for these diseases.

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References

Wagner M, Trauner M . Transcriptional regulation of hepatobiliary transport systems in health and disease: implications for a rationale approach to the treatment of intrahepatic cholestasis. Ann Hepatol. 2005; 4(2):77-99. View

Trussoni C, OHara S, LaRusso N . Correction to: Cellular senescence in the cholangiopathies: a driver of immunopathology and a novel therapeutic target. Semin Immunopathol. 2022; 44(4):545-546. DOI: 10.1007/s00281-022-00930-y. View

Kwong A, Ebel N, Kim W, Lake J, Smith J, Schladt D . OPTN/SRTR 2020 Annual Data Report: Liver. Am J Transplant. 2022; 22 Suppl 2:204-309. DOI: 10.1111/ajt.16978. View

Byun S, Kim D, Ryerson D, Kim Y, Sun H, Kong B . Postprandial FGF19-induced phosphorylation by Src is critical for FXR function in bile acid homeostasis. Nat Commun. 2018; 9(1):2590. PMC: 6030054. DOI: 10.1038/s41467-018-04697-5. View

Malpique R, Ehrhart F, Katsen-Globa A, Zimmermann H, Alves P . Cryopreservation of adherent cells: strategies to improve cell viability and function after thawing. Tissue Eng Part C Methods. 2009; 15(3):373-86. DOI: 10.1089/ten.tec.2008.0410. View

Haep N, Florentino R, Squires J, Bell A, Soto-Gutierrez A . The Inside-Out of End-Stage Liver Disease: Hepatocytes are the Keystone. Semin Liver Dis. 2021; 41(2):213-224. PMC: 8996333. DOI: 10.1055/s-0041-1725023. View

Cai S, Ouyang X, Chen Y, Soroka C, Wang J, Mennone A . Bile acids initiate cholestatic liver injury by triggering a hepatocyte-specific inflammatory response. JCI Insight. 2017; 2(5):e90780. PMC: 5333973. DOI: 10.1172/jci.insight.90780. View

Schimming J, Ter Braak B, Niemeijer M, Wink S, van de Water B . System Microscopy of Stress Response Pathways in Cholestasis Research. Methods Mol Biol. 2019; 1981:187-202. DOI: 10.1007/978-1-4939-9420-5_13. View

de Vries A, Janse M, Blokzijl H, Weersma R . Distinctive inflammatory bowel disease phenotype in primary sclerosing cholangitis. World J Gastroenterol. 2015; 21(6):1956-71. PMC: 4323476. DOI: 10.3748/wjg.v21.i6.1956. View

10.

Brassea-Perez E, Hernandez-Camacho C, Labrada-Martagon V, Vazquez-Medina J, Gaxiola-Robles R, Zenteno-Savin T . "Oxidative stress induced by phthalates in mammals: State of the art and potential biomarkers". Environ Res. 2022; 206:112636. DOI: 10.1016/j.envres.2021.112636. View

11.

Cai S, Boyer J . Studies on the mechanisms of bile acid initiated hepatic inflammation in cholestatic liver injury. Inflamm Cell Signal. 2017; 4(2). PMC: 5553904. View

12.

Trauner M, Boyer J . Bile salt transporters: molecular characterization, function, and regulation. Physiol Rev. 2003; 83(2):633-71. DOI: 10.1152/physrev.00027.2002. View

13.

Tabibian J, Trussoni C, OHara S, Splinter P, Heimbach J, LaRusso N . Characterization of cultured cholangiocytes isolated from livers of patients with primary sclerosing cholangitis. Lab Invest. 2014; 94(10):1126-33. PMC: 4184949. DOI: 10.1038/labinvest.2014.94. View

14.

Ye X, Zhang T, Han H . PPARα: A potential therapeutic target of cholestasis. Front Pharmacol. 2022; 13:916866. PMC: 9342652. DOI: 10.3389/fphar.2022.916866. View

15.

Gulamhusein A, Hirschfield G . Primary biliary cholangitis: pathogenesis and therapeutic opportunities. Nat Rev Gastroenterol Hepatol. 2019; 17(2):93-110. DOI: 10.1038/s41575-019-0226-7. View

16.

Woolbright B, Jaeschke H . Inflammation and Cell Death During Cholestasis: The Evolving Role of Bile Acids. Gene Expr. 2019; 19(3):215-228. PMC: 6827039. DOI: 10.3727/105221619X15614873062730. View

17.

Faccioli L, Kocas-Kilicarslan Z, Diaz-Aragon R, Motomura T, Amirneni S, Malizio M . Human Hepatocytes Isolated from Explanted Livers: A Powerful Tool to Understand End-stage Liver Disease and Drug Screening. Organogenesis. 2022; 17(3-4):117-125. PMC: 9208801. DOI: 10.1080/15476278.2021.1992216. View

18.

Terry C, Hughes R, Mitry R, Lehec S, Dhawan A . Cryopreservation-induced nonattachment of human hepatocytes: role of adhesion molecules. Cell Transplant. 2007; 16(6):639-47. DOI: 10.3727/000000007783465000. View

19.

Gijbels E, Pieters A, De Muynck K, Vinken M, Devisscher L . Rodent models of cholestatic liver disease: A practical guide for translational research. Liver Int. 2021; 41(4):656-682. PMC: 8048655. DOI: 10.1111/liv.14800. View

20.

Tovey M, Gugenheim J, Guymarho J, Blanchard B, Broecke C, GRESSER I . Genes for interleukin-1, interleukin-6, and tumor necrosis factor are expressed at markedly reduced levels in the livers of patients with severe liver disease. Autoimmunity. 1991; 10(4):297-310. DOI: 10.3109/08916939109001904. View