METTL14 promotes glomerular endothelial cell injury and diabetic nephropathy via m6A modification of α-klotho

Molecular Medicine

Manna Li¹  Gaosi Xu¹  Le Deng¹ 

[1] Department of Nephrology, The Second Affiliated Hospital to Nanchang University, No. 1, Minde Road, Donghu District, 330006, Nanchang, China;

关键词: Diabetic nephropathy;    Glomerular endothelial cell injury;    m6A;    METTL14;    α-Klotho;   

DOI  :  10.1186/s10020-021-00365-5

来源: Springer

【 摘 要 】

BackgroundN6-Methyladenosine (m6A) modification has been implicated in many bioprocesses. However, its functions in diabetic nephropathy (DN) have not been determined. Here, we investigated the role of METTL14, a key component of the m6A methyltransferase complex, in DN.MethodsThe expression of METTL14 was detected in DN patients and human renal glomerular endothelial cells (HRGECs). In vitro and in vivo experiments were performed to explore the functions of METTL14 on high glocse-induced HRGECs and renal injury of DN mice. We also investigated whether METTL14 works by regulating α-klotho expression through m6A modification.ResultsMETTL14 were highly expressed in kidneys of DN patients and high glocse-induced HRGECs both at the mRNA and protein level. Overexpression of METTL14 increased ROS, TNF-α and IL-6 levels and apoptosis in HRGECs. Conversely, METTL14 silence decreased the levels of ROS, TNF-α and IL-6 and cell apoptosis. We confirmed that METTL14 down-regulated α-klotho expression in an m6A-dependent manner. In addition, we also found that METTL14 aggravated renal injury and inflammation of db/db mice, which could partially rescued by α-klotho.ConclusionOur data revealed that METTL14 plays a vital role in high glucose-induced glomerular endothelial cells and diabetic nephropathy through m6A modification of α-klotho.

【 授权许可】

CC BY