Canagliflozin and irbesartan ameliorate renal fibrosis via the TGF-β1/Smad signaling pathway in Dahl salt-sensitive rats

Jianlong Zhai, Zhongli Wang, Tingting Zhang, Lili He, Sai Ma, Qingjuan Zuo, Guorui Zhang, Xinyu Wang, Yifang Guo

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: This study assessed the antifibrotic effects of canagliflozin, with or without irbesartan, on renal injury in Dahl salt-sensitive (SS) rats fed a high-salt (HS) diet. Methods: After the preconditioning stage, Dahl SS rats (n = 47) were divided into five experimental groups as follows: low-salt (LS, n = 7), HS (n = 10), HS with canagliflozin (n = 10), HS with irbesartan (n = 10), and HS with canagliflozin and irbesartan (n = 10). Results: The HS diet increased systolic blood pressure (SBP), renal fibrosis, fibrotic protein expression, and transforming growth factor-β1 (TGF-β1)/Smad2/3 pathway protein expression compared with the findings in the LS group. Irbesartan reduced SBP and slowed the loss of renal function. Canagliflozin significantly reduced body weight and renal fibrosis and suppressed the TGF-β1/Smad2/3 pathway. The combined therapy exerted better renoprotective effects on all outcome parameters. Conclusions: These results indicate that canagliflozin and irbesartan exert different effects on renal injury in SS hypertensive rats, and the combined regimen could have stronger effects than either monotherapy.

Original languageEnglish
JournalJournal of International Medical Research
Volume51
Issue number10
DOIs
StatePublished - Oct 2023
Externally publishedYes

Keywords

  • angiotensin II receptor blocker
  • blood pressure
  • Dahl salt-sensitive rat
  • hypertension
  • renal fibrosis
  • Smad2/3
  • sodium-glucose cotransporter 2 inhibitor
  • transforming growth factor-β1

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