Table 1.

Summary list of the roles of SP/KLF transcription factors in various hepatic diseases. (Abbreviations: CCL4: Carbon tetrachloride, CSE: Cystathionine gamma-lyase, EMT: Epithelial-mesenchymal transition, HCC: hepatocellular carcinoma, HFD: High-fat diet, HSC: Hepatic stellate cells, HULC: Highly upregulated in liver cancer, MALAT1: Metastasis Associated Lung Adenocarcinoma Transcript 1, MMP-9: Matrix metalloproteinase 9, NAFLD: Non-alcoholic fatty liver disease, NR0B2: Nuclear receptor subfamily 0, group B, member 2, PCNA: Proliferating cell nuclear antigen, PGC-1α: Peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha, PON1: Paraoxonase-1, PPARα: Peroxisome proliferator-activated receptor α, Ras GRP1: RAS guanyl-releasing protein 1, RYBP: RING1 and YY1-binding protein, SREBP-1c: Sterol regulatory element binding protein-1c, TERT: Telomerase reverse transcriptase, TGF-β: Transforming growth factor β, Twist2: Twist Family BHLH Transcription Factor 2, zDHHC7: Zinc finger DHHC-type palmitoyltransferase 7). Arrow symbol ↑ denotes increase, ↓—decrease and →—connection between two events.

Transcription Factor	Insulin Resistance/NAFLD	HCC	Hepatic Fibrosis	Biliary Cholangitis	Hepatitis	Drug Induced Hepatotoxicity	Acute Liver Toxicity/Failure
SP1	↑ SREBP-1c → ↑ Hepatic lipogenesis [150] ↓ Methylation of PON1 promoter → ↑ NAFLD [151]	↑ RasGRP1, RYBP, CSE, TERT → ↑ HCC [152,153] ↑ HULC and MALAT1 lncRNAs → ↑ HCC [154,155] ↑ Bak → ↓ HCC [156]	↑ TGF-β → ↑ Fibrosis [157]	-	↑ HBV ccc DNA replication → ↑ Hepatitis B [158]	-	↑ TGF-β → ↑ Liver failure [159]
SP3	-	↑ HULC and MALAT1 lncRNAs and ↓ SP1-Bak induction →↑ HCC [154,155,156]	-	-	-	-	-
KLF2	↑ CD36 → ↑ steatohepatitis [72] Predicted link to fibrotic NASH (by IPA analysis of GSE130970) [160]	↓ Hedgehog and TGF-β → ↓ HCC [161] ↑ c-Myc → ↑ HCC [162]	-	-	-	-	↑ Activin A secretion → ↑ Hepatic damage [146]
KLF3	↓ Fam132a → ↑ Insulin resistance [53]	-	-	-	-	-	-
KLF4		↓ Slug → ↓ EMT → ↓ HCC [163]	↑ TGF-β and ↑MMP/TIMP → ↑ Fibrosis [164]	-	-	-	↑ Liver regeneration → ↓ Liver damage [165,166]
KLF5	-	↑ PI3K/Akt/Snail → ↑ EMT → ↑ HCC [167]	-	↑ Ductal regeneration → ↓ Cholangitis [168].	-	-	-
KLF6	↓miR10b → ↑ PPARα → ↑ Trb3→ ↑ Insulin resistance [76] KLF6-IVS1-27Gwt (no splicing) → ↑ KLF6-IVS1-27G>A (splice variant) →↓ NAFLD [54]	↓ PCNA, MMP-9 → ↓ HCC [169] ↓ p53 and↑ BCL-XL → ↑HCC [170]	↑ α1 collagen → ↑HSC activation → ↑ Fibrosis [171]	↓ NR0B2 → ↑ Bile duct ligation induced hepatic injury [109]	-	↑ Diclofenac induced hepatotoxicity [172]	↑ Autophagy → ↑ Hepatic damage [173]
KLF8	-	↑ Wnt/β-catenin → ↑ HCC [174]	-	-	-	-	-
KLF9	↑ CD36 → ↑ Steatohepatitis [77] ↑ PGC-1α → ↑ Hepatic gluconeogenesis → ↑ Insulin resistance [55] ↑ PGC-1α → ↑ Glucocorticoid induced diabetes [55]	-	-	-	-	-	-
KLF10	↑ Pepck → ↑ Hepatic gluconeogenesis → ↑ Insulin resistance [57] ↑ zDHHC7 → ↑ CD36 mediated FA uptake → ↑ Steatohepatitis [80] ↓ Hepatocyte apoptosis → ↓ Steatohepatitis by methionine and choline deficient diet [175]	-	↓ TGF-β → ↓Fibrosis [79]	-	-	-	-
KLF11	↑ FA oxidation → ↓ Steatohepatitis [81] ↓ PEPCK, PGC1A → ↓ Hepatic gluconeogenesis [61]	-	-	-	-	-	-
KLF13	↑ Expression → ↑ NAFLD in humans [23]	↑ Cholesterol synthesis → ↑ HCC [176]	-	-	-	-	-
KLF14	↑ PGC-1α → ↑ Hepatic gluconeogenesis → ↑ Insulin resistance [59] ↑ PI3K/Akt → ↑ Hepatic insulin sensitivity [82] Gene polymorphism in KLF14 → ↑ type II diabetes [177]	-	-	-	-	-	-
KLF15	↑Twist2 → ↓ Steatohepatitis [178] ↑ Recruitment of RIP40 corepressor to the SREBF-1 promoter → ↓ Hepatic lipogenesis [86] ↑ ER stress → ↑ Insulin resistance [85]	-	-	-	↑ Core and surface genes expression → ↑Hepatitis B [179]	-	↓ p38 MAPK/ERK1/2 → ↓ Hepatic injury [180]
KLF16	↑ PPARα → ↑ FA oxidation → ↓ Steatohepatitis and NAFLD [84]	-	-	-	-	-	-