| Literature DB >> 30246318 |
Changhu Lee1, Min Kim1,2, Jun Ho Lee1, Jiyoung Oh1, Hyun-Hee Shin1, Sang Min Lee1, Philipp E Scherer3, Hyug Moo Kwon1, Jang Hyun Choi1, Jiyoung Park1.
Abstract
Extracellular matrix dysregulation is associated with chronic liver disease. CollagenVI-alpha3 chain (COL6A3) is a biomarker for hepatic fibrosis and poor prognosis of hepatocellular carcinoma (HCC), but its function in liver pathology remains unknown. High levels of COL6A3 and its cleaved product, endotrophin (ETP) in tumor-neighboring regions are strongly associated with poor prognosis in HCC patients. Here, we report that the high levels of ETP in injured hepatocytes induce JNK-dependent hepatocyte apoptosis and activate nonparenchymal cells to lead further activation of hepatic inflammation, fibrosis, and apoptosis. Nevertheless ETP per se showed limited phenotypic changes in normal liver tissues. Furthermore, inhibition of ETP activity by utilizing neutralizing antibodies efficiently suppressed the pathological consequences in chronic liver diseases. Our results implicate ETP mechanistically as a crucial mediator in reciprocal interactions among various hepatic cell populations in the pathogenesis of chronic liver disease, and it could be a promising therapeutic target particularly in individuals with high local levels of COL6A3.Entities:
Keywords: JNK pathway; apoptosis; chronic liver disease; collagen VI A3; endotrophin; fibrosis; inflammation; pathology
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Year: 2018 PMID： 30246318 DOI： 10.1002/path.5172
Source DB: PubMed Journal: J Pathol ISSN： 0022-3417 Impact factor: 7.996