TABLE 3.
The role of PRMTs in renal injury, repair and fibrosis.
| Pathological processes | Targets | Models | Functions and mechanisms | References |
|---|---|---|---|---|
| AKI | PRMT5 | HK-2cells; I/R induced AKI | Downregulate Nrf2/HO-1; Increases ROS-induced apoptosis and inflammation; Inhibit tubule cell proliferation | Zakrzewicz et al. (2011) |
| PRMT1,ADMA | I/R induced AKI | Suppress the production of eNOS and NO, Resulte in necrosis of renal capillaries and tubular cells | Tewary et al. (2019), Wu et al. (2021) | |
| CKI(DN) | PRMT1 | rat mesangial cell line | Mediate lipotoxicity-induced apoptosis in mesangial cell; Activate ER stress | Chen et al. (2019) |
| PRMT1 | PTEC cell line, HK2 cells | Induce ER stress and apoptosis through activating PERK and ATF6; Activate EMT activation; Alleviate both tissue injury and renal fibrosis | Wu et al. (2021) | |
| CKI(Hypertension) | ADMA | 5/6Nx | Reduce NO production | Lei et al. (2022) |
| Enhance vascular endothelial dysfunction | ||||
| Repair | PRMT5 | RPTEC; IRI | Enhance the proliferation of tubular cells | Dong et al. (2021) |
| PRMT1 | 2K1C rat model | Prohibit NCK production of ROS and ADMA by suppressing PRMT1 expression to protect the kidney | Guccione et al. (2007) | |
| ADMA | I/R Model with SD rats | Promote endothelial function recovery and decrease renal inflammatory response by suppressing DDAH | Hu et al. (2020) | |
| Fibrosis | PRMT1 | NRK-49F and HK2 cells; UUO | Reduce H4R3me2a expression, Decrease ADMA production, increase NO, and promote renal fibrosis through blockade of PRMT1 | Dong et al. (2018) |
| PRMT1 | UUO | Downregulate DDAH, increased ADMA and reduced renal fibrosis via blocking PRMT1 | Qi et al. (2002) | |
| PRMT1 | UUO; NRK-49F cells | Reduce renal fibroblast activation by downregulating TGF-β/Smad3 pathway to attenuate renal fibrosis with inhibitating PRMT1 | Yang et al. (2019) | |
| PRMT3 | UUO, FA | Increase H4R3me2a expression | Hatanaka et al. (2017) |
2K1C, two-kidney, one-clip rat model; ADMA, asymmetric dimethylarginine; AKI, acute kidney injury; ATF6, activating transcription factor 6; BTG1, B-cell translocation gene 1; ccRCC, clear cell renal cell carcinoma; DDAH, dimethylarginine dimethylaminohydrolase; DN, diabetic nephropathy; EMT, epithelial-to-mesenchymal transition; eNOS, endothelial nitric oxide synthase; ER, endoplasmic reticulum; H4R3me2a, histone H4 arginine 3 asymmetric demethylation; HK2, human kidney 2; IRI, renal ischemia with reperfusion injuries; I/R, ischemia/reperfusion; NCK, non-clipped kidney; Nrf2/HO-1, NF-E2-related factor/heme oxygenase-1; NO, nitric oxide; NRK-49F, normal rat kidney 49F cells; Nx, 5/6 nephrectomy; PERK, protein kinase RNA-like endoplasmic reticulum kinase; PRMTs, Protein arginine methyltransferases; ROS, reactive oxygen species; RPTEC, human renal proximal tubule epithelial cells; SD, Sprague-Dawley; SREBP1, sterol regulatory element-binding protein 1; TGF-β1, transforming growth factor; UUO, unilateral ureter ligation.