Targeting METTL16 attenuates mesangial cell viability and fibrosis in a high-glucose state by suppressing m6A modification and the expression of RAP1B.

BACKGROUND: Methyltransferase-like 16 (METTL16) is involved in regulating kidney disease progression. This study aimed to investigate the effect of METTL16 on the progression of diabetic kidney disease (DKD) and its potential mechanism. METHODS: SV40-MES13 cells were transfected with METTL16 siRNA (siMETTL16), scramble control (siNC), or RAP1B siRNA (siRAP1B) under low glucose (LG) or high glucose (HG) conditions. Subsequently, RNA immunoprecipitation (RIP) assays, cell viability assays, EdU staining, TUNEL staining, ROS staining, and MDA detection were carried out. RESULTS: In SV40-MES13 cells, cell viability, the number of EdU-positive cells, the MDA level, METTL16 mRNA, and protein levels were greater in the HG groups than in the control group. Moreover, cell viability, the number of EdU-positive cells, and VIMENTIN protein levels were lower, whereas the apoptosis rate and ROS and MDA levels were greater in the HG + siMETTL16 group than in the HG + siNC group. RAP1B mRNA and protein levels and N6-methyladenosine modification levels were greater in the HG group than in the control group but lower in the HG + siMETTL16 group than in the HG + siNC group. Furthermore, the METTL16 protein bound to the RAP1B mRNA. Compared with those in the HG + siNC group, cell viability, the number of EdU-positive cells, and VIMENTIN protein levels were decreased, whereas the ROS and MDA levels were increased in the HG + siRAP1B group. CONCLUSION: METTL16 knockdown attenuates cell viability and fibrosis by reducing m6A modification and the expression of RAP1B in high glucose-treated mesangial cells, suggesting the potential of METTL16 as a treatment target for DKD.