Table 2.
Histone methyltransferase inhibition in kidney diseases.
| KMTs | Histone targets | Inhibitors or Knockout mice | Model | Effects | References |
|---|---|---|---|---|---|
| EZH2 | H3K27 | 3-DZNeP | UUO | Inhibits renal fibroblast activation and EMT, alleviates renal fibrosis | (Zhou et al., 2016; Zhou et al., 2018a) |
| 3-DZNeP | I/R or FA induced AKI | Alleviates AKI and reduces renal tubular cell death | (Zhou et al., 2018b) | ||
| 3-DZNeP | Cisplatin induced AKI | Protects against renal tubular cell death, inhibits AKI | (Ni et al., 2019) | ||
| 3-DZNeP | Hyperuricemia-induced CKD | Inhibits fibroblast activation and proliferation, attenuates renal injury | (Shi et al., 2019) | ||
| 3-DZNeP KO mice EPZ-6438, KO mice | STZ-induced DN, Adriamycin nephrotoxicity, SNx | Induces podocyte injury, increases oxidative stress and proteinuira Sensitize mice to glomerular disease increase podocyte injury and dedifferentiation | (Siddiqi et al., 2016) | ||
| Same models as above | Sensitize mice to glomerular disease increase podocyte injury and dedifferentiation | (Majumder et al., 2018) | |||
| GSK126 | Rat renal interstitial fibroblast cells | Inhibits activation of cultured renal interstitial fibroblasts | (Zhou et al., 2016) | ||
| G9a | H3K9 | BIX01294 | UUO | Attenuates renal fibrosis and retains klotho expression | (Irifuku et al., 2016) |
| SUV39H1 | H3K9 | Chaetocin | Mesangial cells | Increases fibronectin and p21expression | (Lin et al., 2016) |
| SET7/9 | H3K4 | Sinefungin | UUO | Ameliorates renal fibrosis; Suppresses peritoneal fibrosis | (Sasaki et al., 2016) |
| DOT1L | H3K79 | EPZ5676 | UUO | Inhibits renal fibroblast activation and EMT; attenuates renal fibrosis | (Liu et al., 2019) |
| SMYD2 | H3K4;H3K36 | AZ505 KO mice | Hypomorphic Pkd1nl/nl mice | Delay cyst growth in ADPKD, reduce activation of STAT3 and NF-κB | (Li et al., 2017) |
DN, Diabetic nephropathy; STZ, streptozotocin; CKD, chronic kidney disease; UUO, unilateral ureteral obstruction; SNx, subtotal nephrectomy; KO, knockout mice; AKI, acute kidney injury; EMT; epithelial–mesenchymal transition; ADPKD, autosomal dominant polycystic kidney disease; STAT3, signal transducer and activator of transcription 3; NF-κB, nuclear factor kappa light chain enhancer of activated B cells.