FTO‐mediated m6A modification of SOCS1 mRNA promotes the progression of diabetic kidney disease

作者：Qiang Sun, Houfa Geng, Meng Zhao, Yang Li, Xi Chen, Qian Sha, Peng Lai, Daoquan Tang, Dongzhi Yang, Jun Liang, Mengzhe Guo · 发表于：Clinical and Translational Medicine · 年份：2022 · DOI：10.1002/ctm2.942 · 被引用次数：29 · 研究领域：RNA modifications and cancer、Cancer-related gene regulation、Cancer-related molecular mechanisms research

N6-methyladenosine (m6A) is the most prominent and frequent internal messenger RNA (mRNA) modification and plays diverse roles in regulating functions of modified transcripts.1 However, the role of m6A modification in kidney disease remains rarely understood, especially at the onset of diabetic kidney disease (DKD).2 Here, we delineate the biological role of FTO-mediated m6A modification in DKD through imaging mass cytometry (IMC), LC/MS, and RNASeq methods. The results show that the loss of m6A levels by overexpressing FTO recapitulated human DKD by increasing the expression of suppressors of cytokine signalling 1 (SOCS1) protein level to alleviate inflammation response and kidney injury. Thus, FTO maybe a potential therapeutic target for DKD patients. To quantify the m6A level at cellular and spatial levels, we designed an IMC panel specific to kidney histology and used this to analyse kidney biopsies (Figure 1A and Table S1). IMC integrates IHC using metal isotope-tagged antibodies with laser ablation and mass-spectrometry-based detection to produce high-dimensional images,3 which allow simultaneously quantified the m6A levels and its regulators. We identified 17 676 cells and quantified the levels of m6A, regulators, and spatial characteristics at single-cell level (Figures 1 and S1). We identified five dominant cell clusters of proximal tubules, distal convoluted tubule, glomerulus (Glom) endothelial, macrophage, and stromal cell populations.4 IMC and IHC data demonstrat...