Autophagy, Mitophagy and MicroRNA Expression in Chronic Hepatitis C and Autoimmune Hepatitis
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ORIGINAL ARTICLE
Autophagy, Mitophagy and MicroRNA Expression in Chronic Hepatitis C and Autoimmune Hepatitis Tímea Szekerczés 1 & Alíz Gógl 1 & Ildikó Illyés 1 & József Mandl 2 & Katalin Borka 1 & András Kiss 1 & Zsuzsa Schaff 1 & Gábor Lendvai 1 & Klára Werling 3 Received: 8 November 2019 / Accepted: 11 February 2020 # The Author(s) 2020
Abstract Although the role of autophagy has been implicated in several forms of chronic hepatitis, it is still not fully understood. Active autophagy eliminates damaged molecules and organelles (such as mitochondria) by lysosomal degradation. In the present study, we aimed to examine and compare autophagy activity in chronic hepatitis C (CHC) and autoimmune hepatitis (AIH) by detecting the expression of autophagy (LC3 and p62) and mitochondrium-related (TOMM20) proteins, as well as the levels of selected microRNAs (miR-101, -155, -204 and − 224) known to be involved in the regulation of autophagy. In addition, the expression levels were related to pathohistological parameters. Liver biopsy samples, including 45 CHC and 18 AIH cases, were immunohistochemically stained for LC3, p62 and TOMM20 and the expression of miRNAs was determined using real-time PCR. We found elevated LC3 and p62 in AIH samples as compared with CHC ones, indicating an activated autophagy that is impaired in AIH as no degradation of p62 seemed to occur. Moreover, p62 showed strong correlation with necroinflammatory grades in the AIH group. The observed elevated levels of TOMM20 and p62 suggest a less efficient elimination of damaged mitochondria in AIH as opposed to CHC, in which autophagy seems to have a more active function. The level of miR-101 was increased in case of CHC as compared with AIH, however, miR-155, -204 and 224 resulted in no expressional. Furthermore, miR-224 level correlated with steatosis and miR-155 expression with fibrosis stage in CHC. In conclusion, dissimilar autophagic activity was observed in CHC and AIH, suggesting a close association between impaired autophagy and severity of necroinflammation. This impairment may not be regulated by the analyzed miRNAs. Nevertheless, miR-224 and − 155 seem to be associated with CHC progression. Keywords Chronic hepatitis . autophagy . mitophagy . microRNA . immunohistochemistry
Introduction Hepatitis C virus (HCV) infection is one of the main health problems affecting 71 million people worldwide [1]. Despite the remarkable healing effect of the newly introduced directGábor Lendvai and Klára Werling contributed equally to the study. * Gábor Lendvai [email protected] 1
2nd Department of Pathology, Semmelweis University, Üllői 93, 1091 Budapest, Hungary
2
Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, 1094 Budapest, Hungary
3
2nd Department of Internal Medicine, Semmelweis University, 1088 Budapest, Hungary
acting antivirals (DAAs), several issues are still not resolved or are under dispute [2, 3]. One of these is the role autophagy may play in the pathogenesis of chronic h
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