Schilcher, Katharina and Dayoub, Rania and Kubitza, Marion and Riepl, Jakob and Klein, Kathrin and Buechler, Christa and Melter, Michael and Weiss, Thomas S. (2023) Saturated Fat-Mediated Upregulation of IL-32 and CCL20 in Hepatocytes Contributes to Higher Expression of These Fibrosis-Driving Molecules in MASLD. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 24 (17): 13222. ISSN 1661-6596, 1422-0067
Full text not available from this repository. (Request a copy)Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) comprises a spectrum of liver diseases, ranging from liver steatosis to metabolic dysfunction-associated steatohepatitis (MASH), increasing the risk of developing cirrhosis and hepatocellular carcinoma (HCC). Fibrosis within MASLD is critical for disease development; therefore, the identification of fibrosis-driving factors is indispensable. We analyzed the expression of interleukin 32 (IL-32) and chemokine CC ligand 20 (CCL20), which are known to be linked with inflammation and fibrosis, and for their expression in MASLD and hepatoma cells. RT-PCR, ELISA and Western blotting analyses were performed in both human liver samples and an in vitro steatosis model. IL-32 and CCL20 mRNA expression was increased in tissues of patients with NASH compared to normal liver tissue. Stratification for patatin-like phospholipase domain-containing protein 3 (PNPLA3) status revealed significance for IL-32 only in patients with I148M (rs738409, CG/GG) carrier status. Furthermore, a positive correlation was observed between IL-32 expression and steatosis grade, and between IL-32 as well as CCL20 expression and fibrosis grade. Treatment with the saturated fatty acid palmitic acid (PA) induced mRNA and protein expression of IL-32 and CCL20 in hepatoma cells. This induction was mitigated by the substitution of PA with monounsaturated oleic acid (OA), suggesting the involvement of oxidative stress. Consequently, analysis of stress-induced signaling pathways showed the activation of Erk1/2 and p38 MAPK, which led to an enhanced expression of IL-32 and CCL20. In conclusion, cellular stress in liver epithelial cells induced by PA enhances the expression of IL-32 and CCL20, both known to trigger inflammation and fibrosis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LIVER-REGENERATION; PALMITIC ACID; INFLAMMATION; INTERLEUKIN-32; LIPOTOXICITY; ACCUMULATION; RECEPTOR; HYPOXIA; DISEASE; OBESITY; MASLD; NAFLD; MASH; NASH; steatosis; interleukin 32; chemokine CC ligand 20; oxidative stress; saturated fatty acid; MAPK pathway |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Mar 2024 08:38 |
| Last Modified: | 09 Mar 2024 08:38 |
| URI: | https://pred.uni-regensburg.de/id/eprint/59217 |
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