DMM inhibited obstruction-induced renal fibrosis by blunting inflammation and activating PPAR signaling

To understand the roles and mechanisms of DMM in unilateral ureteral obstruction (UUO)-induced renal fibrosis, we performed RNA sequencing of UUO kidneys from mice treated with or without dimethyl malonate (DMM). DMM administration led to metabolic reprogramming in obstructed kidneys, the genes associated with the metabolism of fatty acid, organic acid, cellular amino acid, and mitochondrial function were significantly upregulated. Conversely, the downregulated genes in DMM-treated mice were involved in inflammation, including T cell immunity. Moreover, the upregulated genes in DMM-treated mice were associated with PPAR signaling. The RNA-seq analysis suggests that DMM activated PPAR and metabolic pathways while inhibited inflammatory signalings.