Comprehensive and Combined Omics Analysis Reveals Factors of Ischemia-Reperfusion Injury in Liver Transplantation

Abstract

Aim: To explore molecular mechanisms underlying liver ischemia-reperfusion injury (IRI). Materials & methods: Four Gene Expression Omnibus datasets comprising liver transplantation data were collected for a comprehensive analysis. A proteomic analysis was performed and used for correlations analysis with transcriptomic. Results & conclusion: Ten differentially expressed genes were co-upregulated in four Gene Expression Omnibus datasets, including ATF3, CCL4, DNAJB1, DUSP5, JUND, KLF6, NFKBIA, PLAUR, PPP1R15A and TNFAIP3. The combined analysis demonstrated ten coregulated genes/proteins, including HBB, HBG2, CA1, SLC4A1, PLIN2, JUNB, HBA1, MMP9, SLC2A1 and PADI4. The coregulated differentially expressed genes and coregulated genes/proteins formed a tight interaction network and could serve as the core factors underlying IRI. Comprehensive and combined omics analyses revealed key factors underlying liver IRI, and thus having potential clinical significance.

Resolving the graft ischemia-reperfusion injury during liver transplantation at the single cell resolution

“…We annotated the four CLEC4G + PECAM1 low clusters as LSEC based on previous studies 14, [21][22][23] regulation related functions 26,27 . Compared to TMo clusters, the interactions between KC and endothelial cell clusters were specifically enriched in HLA−C_FAM3C, CCL4_SLC7A1 and CD74_COPA, most of which play an important role in IRI [28][29][30] . 31,32 .…”

“…In addition, ligand-receptor pairs such as HLA−C_FAM3C, CD74_MIF, CD74_COPA, CD74_APP which play an important role in IRI, were enriched in the interaction between KC and B plasma cell clusters [28][29][30] . Compare to the interactions between KC and B cell clusters, those between KC and plasma cell clusters were specifically enriched in CCL4_SLC7A1 and CCL4_GPRC5D which may relate to possible chemotaxis function in KC clusters 36,37 ( Figure 6H).…”

“…Meanwhile, the interactions between mononuclear phagocytes and VEC clusters were enriched in nicotinamide phosphoribosyltransferase (NAMPT) related, CD44_SELE and other immuneregulation related functions26,27 . Compared to TMo clusters, the interactions between KC and endothelial cell clusters were specifically enriched in HLA−C_FAM3C, CCL4_SLC7A1 and CD74_COPA, most of which play an important role in IRI[28][29][30] .…”

Proteomics in Liver Transplantation: A Systematic Review

“…On the other hand, Coskun et al (35) analyzed cold ischemia using organ preservation solution as a sample source. Three other studies recollected both ischemia and reperfusion samples and compared them to control (pre- ischemia) samples and even between them (18,29,36). When rats were used as a model, Knecht et al (16) carried out ex vivo cold storage and normothermic reperfusion, whereas the other 2 publications performed a model of in vivo selective warm ischemia using vascular clamping followed by reperfusion, such in normal (20) as in steatotic rats (27).…”

Hepatocyte KLF6 expression affects FXR signalling and the clinical course of primary sclerosing cholangitis

“…Beside playing a role in HCC, KLF6 has been established as an important transcription factor in a variety of liver diseases, including hepatic fibrogenesis, acute liver injury, ischaemia reperfusion damage and non‐alcoholic fatty liver diseases (NAFLD) 13‐15 . In the previous studies, we characterized KLF6 as a regulator of autophagy in acute liver injury and as a mediator of hepatic glucose and lipid metabolism in NAFLD by binding directly to the promoter regions of autophagy‐regulating factors and hepatic glucokinase, as well as a post‐transcriptional regulation of peroxisome proliferator activated receptor alpha (PPARα) expression 16‐18 .…”