ESRRA-ATG5-Mediated mitophagy enhances arginine metabolism to alleviate diabetic kidney disease

: AAV: adeno-associated virus; ACR: albumin:creatinine ratio; ACTA2: actin alpha 2, smooth muscle; AKI: acute kidney injury; ALB: albumin; ARG2: arginase 2; ATG12: autophagy related 12; ATG16L1: autophagy related 16-like 1; ATG5: autophagy related 5; BafA1: bafilomycin A1; BUN: blood urea nitrogen; CETSA: cellular thermal shift assay; ChIP-qPCR: chromatin immunoprecipitation followed by quantitative PCR; ChIP-Seq: chromatin immunoprecipitation sequencing; Co-IP: co-immunoprecipitation; CON: control; Cr: creatinine; DEGs: differentially expressed genes; DHE: dihydroethidium; DKD: diabetic kidney disease; eGFR: estimated glomerular filtration rate; ESRD: end-stage renal disease; ESRRA: estrogen related receptor alpha; FSGS: focal segmental glomerulosclerosis; GSEA: gene set enrichment analysis; GTT: glucose tolerance test; HE: hematoxylin and eosin; HFD: high-fat diet; HG: high glucose; HOMA-IR: homeostatic model assessment of insulin resistance; IF: immunofluorescence; IgAN: immunoglobulin A nephropathy; IHC: immunohistochemistry; IOD: integrated optical density; ITT: insulin tolerance test; KD: equilibrium dissociation constant; KEGG: Kyoto Encyclopedia of Genes and Genomes; KO: knockout; LUC: luciferase; MCN: minimal change nephrosis; MST: microscale thermophoresis; MTS: mitochondrial targeting sequence; NAFLD: non-alcoholic fatty liver disease; NIH: National Institutes of Health; NO: nitric oxide; OCR: oxygen consumption rate; PAS: periodic acid-Schiff; PCR: polymerase chain reaction; PINK1: PTEN induced kinase 1; PRKN: parkin RBR E3 ubiquitin protein ligase; qPCR: quantitative PCR; RNA-seq: RNA sequencing; ROS: reactive oxygen species; RT-qPCR: reverse transcription quantitative PCR; SAC: salvianolic acid C; SAFI: salvianolic acid for injection; SDH: succinate dehydrogenase; SEM: standard error of the mean; SPF: specific pathogen-free; SPR: surface plasmon resonance; STZ: streptozotocin; TCA: tricarboxylic acid; TECs: tubular epithelial cells; TEM: transmission electron microscopy; TFAM: transcription factor A, mitochondrial.