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Table 1 Pathway analysis of the commonly affected genes by CsA in WT-PCLS and FXRKO-PCLS

From: Cyclosporin A induced toxicity in mouse liver slices is only slightly aggravated by Fxr-deficiency and co-occurs with upregulation of pro-inflammatory genes and downregulation of genes involved in mitochondrial functions

  Functional category Pathways FDR In Data Total
Upregulation ER stress Endoplasmic reticulum stress response pathway 2.0E-08 16 55
ER stress Role of PKR in stress-induced apoptosis 3.2E-05 12 53
ER stress CFTR folding and maturation (normal and CF) 3.4E-05 8 21
ER stress APRIL and BAFF signaling 2.0E-03 8 39
ER stress ATM/ATR regulation of G1/S checkpoint 3.3E-03 7 32
ER stress Regulation of degradation of deltaF508-CFTR in CF 1.7E-05 11 39
ER stress wtCFTR traffic/ER-to-Golgi (normal) 5.0E-04 6 15
ER stress DeltaF508-CFTR traffic/ER-to-Golgi in CF 5.0E-04 6 15
ER stress RAB1A regulation pathway 1.8E-03 5 12
ER stress DeltaF508-CFTR traffic/Sorting endosome formation in CF 1.8E-03 7 28
ER stress Regulation of degradation of wtCFTR 1.9E-03 6 20
ER stress Proteolysis_Role of Parkin in the Ubiquitin-Proteasomal Pathway 4.3E-03 6 24
ER stress Clathrin-coated vesicle cycle 4.6E-03 10 71
Metabolic diseases Role of free fatty acids in obesity and type 2 diabetes 2.6E-04 10 45
Metabolic diseases Role of ER stress in obesity and type 2 diabetes 9.9E-04 10 54
Inflammation IL-17 signaling pathways 1.8E-03 10 60
Inflammation CD40 signaling 3.0E-03 10 65
Inflammation Role of PKR in stress-induced antiviral cell response 4.4E-03 9 57
Downregulation Coagulation Thromboxane A2 pathway signaling 4.7E-04 13 49
Coagulation Lectin induced complement pathway 4.7E-04 13 49
Coagulation HTR2A-induced activation of cPLA2 1.1E-03 11 43
Coagulation Blood coagulation 1.8E-03 10 39
Coagulation Classical complement pathway 3.4E-03 11 52
Coagulation MIF - the neuroendocrine-macrophage connector 4.2E-03 10 46
Coagulation Alternative complement pathway 4.6E-03 9 39
Regulation of energy metabolism CREB pathway 2.1E-03 11 49
Regulation of energy metabolism Regulation of lipid metabolism by niacin and isoprenaline 3.7E-03 10 45
Regulation of energy metabolism Bile acids regulation of glucose and lipid metabolism via FXR 3.7E-03 9 37
Regulation of energy metabolism PPAR pathway 3.7E-03 12 63
  1. Metacore pathway analysis using significant genes (FDR ≤ 0.05) regulated by CsA in WT-PCLS and FXRKO-PCLS identified 18 significantly upregulated pathways and 11 significantly downregulated pathways (FDR ≤ 0.005). The identified pathways are grouped into functional categories according to MetaCore pathway classification tool and are presented in the first column. Next columns represent names of the identified pathways, FDR score, number of significantly regulated genes identified in our study (“In data”), and the total number of genes belonging to the identified pathways (“Total”)