AI Article Synopsis
- Researchers studied primary hepatic stellate cells (HSCs) from patients with advanced liver fibrosis to discover key genes and proteins involved in liver cirrhosis.
- They analyzed mRNA and protein expression differences using RNA sequencing and mass spectrometry, finding 2156 transcripts and 711 proteins that were differently expressed.
- The study identified 96 overlapping upregulated molecules related to wound healing and cell adhesion, with pyruvate kinase M2 and EH domain-containing 2 emerging as potential new biomarkers for advanced liver cirrhosis.
Article Abstract
Background And Aim: Hepatic fibrosis is a common pathogenic outcome of almost all chronic liver diseases and a growing public health problem globally. However, the key genes or proteins driving liver fibrosis and cirrhosis are not well understood. We aimed to identify novel hepatic fibrosis genes of human primary hepatic stellate cells (HSCs).
Methods: Human primary HSCs were isolated from surgically resected advanced fibrosis liver tissues (n = 6) and surgical resection of normal liver tissue around hemangioma (n = 5). Differences in the expression levels of mRNA and proteins from HSCs in advanced fibrosis group and the control group were analyzed using RNA sequencing and mass spectrometry as transcriptomic and proteomic approaches. The obtained biomarkers were further validated through real-time quantitative polymerase chain reaction (RT-qPCR), immunofluorescence, and Western blot.
Results: A total of 2156 transcripts and 711 proteins were found to be differently expressed between the advanced fibrosis group and the control group patients. The Venn diagram shows that a total of 96 upregulated molecules are overlapped in both the transcriptomic and proteomic datasets. Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes analysis indicated that those overlapped genes were mainly involved in wound healing, cell adhesion regulation, and actin binding, which reflects the major biological conversions in liver cirrhosis process. Pyruvate kinase M2 and EH domain-containing 2 were identified as potential new markers for advanced liver cirrhosis, which have been validated in primary human HSCs and in vitro cellular hepatic fibrosis model Lieming Xu-2 (LX-2) cells.
Conclusions: Our results revealed the major transcriptomic and proteomic changes during liver cirrhosis process and identified new biomarkers and potential therapeutic targets for advanced liver fibrosis.
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| http://dx.doi.org/10.1111/jgh.16221 | DOI Listing |
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