Long noncoding RNA MALAT1 mediates high glucose-induced glomerular endothelial cell injury by epigenetically inhibiting klotho via methyltransferase G9a.

Several recent reporters have indicated the potential role of long noncoding RNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in diabetic nephropathy (DN). However, these studies mainly focus on renal tubular epithelial cells HK-2, the role of MALAT1 in human renal glomerular endothelial cells (HRGECs) remains unclear. Hence, this study aimed to explore the role of MALAT1 in high glucose (HG)-induced HRGECs injury and the underlying epigenetic mechanism. Increased MALAT1 and decreased klotho expression were observed in both renal tissues from DN patients and HG-exposed HRGECs. Furthermore, MALAT1 expression was negatively correlated with klotho expression. Moreover, both MALAT1 knockdown and klotho overexpression significantly abolished the HG-induced HRGECs injury. Importantly, klotho overexpression reversed the MALAT1 overexpression-mediated enhancement of the HG-induced HRGECs injury. In addition, MALAT1 recruited G9a to elevate H3K9me1, which can bind to the klotho promoter and thus inhibited klotho transcription. In conclusion, MALAT recruits methyltransferase G9a to elevate H3K9me1 and epigenetically inhibits klotho expression, and thus mediates HG-induced glomerular endothelial cell injury.