Novel Peptide DR3penA as a Low-Toxicity Antirenal Fibrosis Agent by Suppressing the TGF-ß1/miR-212-5p/Low-Density Lipoprotein Receptor Class a Domain Containing 4/Smad Axis.
ACS Pharmacol Transl Sci
; 7(4): 1126-1141, 2024 Apr 12.
Article
em En
| MEDLINE
| ID: mdl-38633584
ABSTRACT
Renal fibrosis is a complex pathological process that contributes to the development of chronic kidney disease due to various risk factors. Conservative treatment to curb progression without dialysis or renal transplantation is widely applicable, but its effectiveness is limited. Here, the inhibitory effect of the novel peptide DR3penA (DHα-(4-pentenyl)-AlaNPQIR-NH2), which was developed by our group, on renal fibrosis was assessed in cells and mice with established fibrosis and fibrosis triggered by transforming growth factor-ß1 (TGF-ß1), unilateral ureteral obstruction, and repeated low-dose cisplatin. DR3penA preserved renal function and ameliorated renal fibrosis at a dose approximately 100 times lower than that of captopril, which is currently used in the clinic. DR3penA also significantly reduced existing fibrosis and showed similar efficacy after subcutaneous or intraperitoneal injection. Mechanistically, DR3penA repressed TGF-ß1 signaling via miR-212-5p targeting of low-density lipoprotein receptor class a domain containing 4, which interacts with Smad2/3. In addition to having good pharmacological effects, DR3penA could preferentially target injured kidneys and exhibited low toxicity in acute and chronic toxicity experiments. These results unveil the advantages of DR3penA regarding efficacy and toxicity, making it a potential candidate compound for renal fibrosis therapy.
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Base de dados:
MEDLINE
Idioma:
En
Revista:
ACS Pharmacol Transl Sci
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China