PRMT1 mediates podocyte injury and glomerular fibrosis through phosphorylation of ERK pathway.

Diabetic nephropathy (DN) is characterized by a change of glomerular structure and dysfunction of filtration barrier, which significantly accompanied by podocytes apoptosis and glomerular fibrosis. Angiotensin Ⅱ(Ang Ⅱ) induced activation of ERK1/2 signaling plays important roles in causing apoptosis of podocytes in DN kidneys. Previous studies have shown that PRMT1 have a pro-inflammatory function through activating ERK1/2 signaling pathway during development of chronic pulmonary disease, however, its role in DN development has not been investigated. Here, we detected a higher expression of PRMT1 in podocytes of kidneys from DN patients compared with normal kidneys. High glucose administration induced elevation of PRMT1 expression in podocytes, accompanied with higher phosphorylation of ERK and cleaved caspase-3. AMI-1, a selective inhibitor for PRMT1, could block these effects caused by glucose treatment. Administration of AMI-1 also attenuated apoptosis of podocytes during DN development of high-fatty diet-induced diabetic mice. Epithelial to mesenchymal transition during DN development, which characterized by extracellular matrix deposition in podocytes, was also restrained by AMI-1 treatment. Collectively, this study firstly demonstrated that PRMT1 exert podocyte-injury effects in mouse glomerulus through Ang Ⅱ/ERK pathway, which reveals a potential therapeutic target for DN.