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. 2023 Mar 17;8:129. doi: 10.1038/s41392-023-01379-7

Table 2.

Histone methylation and methyltransferases in kidney fibrosis

Methyltransferase Histone site Interventions Experimental model Results Ref.
DOT1L H3K79me2 EPZ5676 UUO TGF-β↓, G2/M arrest↓, Snail↓, Twist↓, Notch↓, SMAD3↓, EGFR↓, PDGFR↓, STAT3↓, AKT↓, NF-κB↓, KLOTHO↑, SMAD7↑ 289
H3K79 EPZ004777 IRI ROS↓, PI3K/AKT↓ 290
G9a H3K9me1 BIX01294 UUO α-SMA↓, fibronectin↓, KLOTHO↑ 291
SMYD2 H3K36me3 AZ505 UUO SMAD3↓, ERK1/2↓, AKT↓, STAT3↓, NF-kB↓, Snail↓, Twist↓, SMAD7↑ 292
SETD7 H3K4 PFI-2 folic acid, UUO M2 macrophages-myofibroblasts transition↓, myeloid fibroblasts activation↓, inflammation↓ 293
H3K4me1 sinefungin UUO mesenchymal markers↓, ECM↓ 294
H3K4me2 - type 1 diabetes (STZ) Col1a↑ 295
SUV39H1 H3K9me2 - type 1 diabetes (STZ) Col1a↑ 295
EZH2 H3k27me3 3-DZNeP, GSK126 UUO SMAD7↑, PTEN↑ 296
H3k27me3 3-DZNeP hyperuricemia serum uric acid↓, XOD↓, TGF-β/Smad3↓, EGFR↓, ERK1/2↓, EMT↓, apoptosis↓, fibroblast activation↓, ECM↓, NF-κB↓ 297
H3k27me3 GNA UUO, folic acid Smad7↑, TGF-β/Smad3↓, α-SMA↓, fibronectin↓, collagens↓ 298
PRMT1 H4R3Me2a AMI-1 UUO TGF-β/Smad3↓ 299
MLL1/WDR5 H3K4me3 MM-102, OICR-9429 IRI p16↓ 300

AKT protein kinase B, α-SMA alpha-smooth-muscle actin, Col1a collagen-1α, DOT1L disruptor of telomeric silencing 1-like, ECM extracellular matrix, EGFR epidermal growth factor receptor, EMT epithelial-to-mesenchymal transition, ERK extracellular signal-regulated kinase, EZH2 enhancer of zester homolog 2, GNA gambogenic acid, IRI ischemia-reperfusion injury, MLL1 mixed-lineage leukemia 1, NF-κB nuclear factor kappa B, PI3K phosphatidylinositol 3-kinase, PDGFR platelet-derived growth factor receptor, PRMT-1 protein arginine methyltransferase 1, PTEN phosphatase and tensin homolog, ROS reactive oxygen species, STED7 SET domain containing 7 histone lysine methyltransferase, SMYD2 SET and MYND domain containing 2, STAT3 signal transducer and activator of transcription 3, STZ streptozotocin, TGF-β transforming growth factor beta, UUO unilateral ureteral occlusion, WDR5 WD repeat domain 5, XOD xanthine oxidase, 3-DZNeP 3-deazaneplanocin A