Table 2.
Representative studies on taking drug repurposing or targeting the key regulatory molecules involved in lipid metabolism to treat renal fibrosis.
| Target | Experimental model | Intervention manner | Involved lipid metabolism improvement | Fibrosis amelioration | Ref |
|---|---|---|---|---|---|
| CD36 | 5/6 nephrectomy with angiotensin II infusion & unilateral ureteral obstruction | Antagonist 5A peptide | Prevent lipid metabolism alteration | Y | [64] |
| CPT1/2 | FAN | CPT1 agonists, C75 | Block FA synthase while resrore CPT1 and ACOX1 expression, hence reinfore FAO | Y | [8] |
| FAN & UUO | CPT1A OE | Prevent mitochondrial function and facilitate FAO | Y | [67] | |
| DN | CPT2 OE | Inhibit AGEs induced FAO surppression | Y | [68] | |
| SREBP1/2 | UUO | Inhibitor, fatostatin | Undetected | Y | [72] |
| DN | Inhibitor, fatostatin | Undetected | N | [74] | |
| PPARs | UUO & remnant kidney model | PPAR-α agonist BAY PP1 | Undetected | Y | [81] |
| age-associated renal fibrosis model | PPARα/β dual agonist MHY2013 | Increase nuclear translocation and activity of PPARα/β and their target genes related to FAO | Y | [82] | |
| FAN | PPAR-α agonist fenofibrate | Restore FAO-related enzymes CPT1A/2 and ACOX1/2 | Y | [8] | |
| Renal Transplant Model | PPAR-α agonist fenofibrate | Undetected | Y | [83] | |
| UUO | PPAR-γ agonist lobeglitazone | Undetected | Y | [84] | |
| TGF-β1 induced renal fibrosis model | PPAR-γ agonist pioglitazone | Undetected | Y | [86] | |
| UUO | PPAR-γ agonist | Undetected | Y | [87] | |
| UUO | PPAR-γ agonist | Undetected | N | [88] | |
| PGC-1α | DKD | Use rosiglitazone as pharmaceutical inducers | Enhance mitochondrial function of energy metabolism | Y | [91] |
| FAN & UUO & APOL1-induced fibrosis models | Genetic re-expression of PGC-1α | Resist Notch induced FAO impairment and mitochondrial dysfunction | Y | [92] | |
| TGF-β1 induced in vitro fibrosis model | PGC-1α-siRNA | Undetected | Y | [94] | |
| PCSK9 | UUO & N-nitro-L-arginine methyl ester mice model | PCSK9Qβ-003 vaccine |
Upregulate FAO-related factors such as CD36, CPT1A, SREBP2, PPAR-α/γ, PGC-1, ACOX1, and LPL |
Y | [98] |
| MiR-21 | UUO & unilateral IRI | KD by Chemically modified ASO | Upregulate PPAR-α to enhance lipid metabolism | Y | [120] |
| Alport nephropathy | KD by Chemically modified ASO | Upregulate PPAR-α and its downstream FA oxidation and mitochondrial/peroxisomal biogenic functions | Y | [121] | |
| miR-9-5p | UUO | lentivirus carrying miR-9-5p mimics |
Regulate CPT1A and PGC-1α to enhance mitochondrial function |
Y | [122] |
| miR-33 | UUO & FAN | pHILP to carry miR33 PNA inhibitors | Increase CPT1A expression and improve FAO | Y | [124] |
| TUG1 | DN | Podocyte-specific OE of TUG1 | Upregulate PGC-1α and modulate mitochondrial bioenergetics | Undetected | [129] |
Y yes, N no, undetected the author detected other pathways such as TGF-β or reactive oxygen species rather than lipid metabolism pathway,
CD36 cluster of differentiation 36, CPT carnitine palmitoyl transferase, SREBP sterol regulatory element-binding protein regulatory element-binding protein 2, PPAR-α peroxisome proliferator-activated receptor α, PPAR-γ peroxisome proliferator-activated receptor γ, PGC-1 peroxisome proliferator-activated receptor gamma coactivator 1, AGEs advanced glycation end products, DN diabetic nephropathy, DKD diabetic kidney disease, UUO unilateral ureteral obstruction, FAN folic acid-induced nephropathy, IRI ischemia-reperfusion injury, ASO antisense oligonucleotide, pHLIP pH low insertion peptide, PNA peptide nucleic acid, KD knock down, OE overexpression, PCSK9 proprotein convertase subtilisin/kexin type 9.