The human liver‐specific proteome defined by transcriptomics and antibody‐based profiling

Abstract

Human liver physiology and the genetic etiology of the liver diseases can potentially be elucidated through the identification of proteins with enriched expression in the liver. Here, we combined data from RNA sequencing (RNA-Seq) and antibody-based immunohistochemistry across all major human tissues to explore the human liver proteome with enriched expression, as well as the cell type-enriched expression in hepatocyte and bile duct cells. We identified in total 477 protein-coding genes with elevated expression in the liver: 179 genes have higher expression as compared to all the other analyzed tissues; 164 genes have elevated transcript levels in the liver shared with at least one other tissue type; and an additional 134 genes have a mild level of increased expression in the liver. We identified the precise localization of these proteins through antibody-based protein profiling and the subcellular localization of these proteins through immunofluorescent-based profiling. We also identified the biological processes and metabolic functions associated with these proteins, investigated their contribution in the occurrence of liver diseases, and identified potential targets for their treatment. Our study demonstrates the use of RNA-Seq and antibody-based immunohistochemistry for characterizing the human liver proteome, as well as the use of tissue-specific proteins in identification of novel drug targets and discovery of biomarkers.-Kampf, C., Mardinoglu, A., Fagerberg, L., Hallström, B. M., Edlund, K., Lundberg, E., Pontén, F., Nielsen, J., Uhlen, M. The human liver-specific proteome defined by transcriptomics and antibody-based profiling.

Comparative proteomic study reveals 17β-HSD13 as a pathogenic protein in nonalcoholic fatty liver disease

“…However, some of the 17β-HSD family members, including 17β-HSD-4, -7, -10, and -12, have been shown to participate in CHO and fatty acid metabolism, suggesting that 17β-HSD13 might also play a role in lipid metabolic pathways. A recent study reported that hepatic up-regulation of 17β-HSD13 was observed in patients with fatty liver, which is consistent with our findings and further supports a role of this enzyme in the pathogenesis of NAFLD (37).…”

Reactive Metabolite-induced Protein Glutathionylation: A Potentially Novel Mechanism Underlying Acetaminophen Hepatotoxicity

“…Remarkably, nearly one-third of glutathionylated proteins in our study were localized in the mitochondria, while mitochondrial proteins typically account for only 7% of the total liver proteome (28). The enrichment of mitochondrial proteins in our dataset agrees with the central role that mitochondrial dysfunction plays in APAP-induced hepatotoxicity (29).…”

Metrics for the Human Proteome Project 2015: Progress on the Human Proteome and Guidelines for High-Confidence Protein Identification

“…The tissues with the most mRNAs highly enriched (at least 5× the levels in all other tissues) are testis (999) and brain (318). Several tissue-specific HPA publications have been published, and more are expected during 2015 with tissue-specific immunohistochemical and transcript evidence to guide specimen selection for further MS studies, for example, describing the brain, 18 liver, 19 testis, 20 kidney, 21 pancreas, 22 skin, 23 adipose tissue, 24 gallbladder, 25 lung, 26 gastrointestinal tract, 27 and cardiac and skeletal muscle. 28 HPA, v14, will be released in Fall 2015 along with a novel Rodent Brain Atlas comprising immunofluorescently stained whole-mouse-brain sections.…”