Losartan ameliorates renal fibrosis by inhibiting tumor necrosis factor signal pathway

Area of Science:

• Nephrology
• Molecular Biology
• Pharmacology

Background:

• Losartan is a common treatment for chronic kidney disease (CKD).
• Its precise mechanism of action in treating CKD remains unclear.
• Identifying the molecular targets of losartan is crucial for understanding its efficacy.

Purpose of the Study:

• To investigate the molecular targets of losartan in the context of CKD.
• To elucidate the mechanism by which losartan ameliorates renal fibrosis.
• To explore the role of the tumor necrosis factor (TNF) signaling pathway in losartan's therapeutic effects.

Main Methods:

• High-throughput sequencing (HTS) was employed to screen potential targets of losartan.
• In vivo (unilateral ureteral obstruction - UUO rat model) and in vitro (human proximal renal tubular epithelial cells - HK-2) experiments were conducted.
• The expression of fibrosis-related genes (COL-1, α-SMA, Vimentin) and the activation of the TNF pathway were assessed.

Main Results:

• HTS identified the tumor necrosis factor (TNF) signaling pathway as a potential target of losartan.
• The TNF pathway was found to be activated in UUO rat kidneys and TGF-β1-treated HK-2 cells.
• Losartan significantly inhibited TNF pathway activation and the expression of fibrosis markers (COL-1, α-SMA, Vimentin).

Conclusions:

• Losartan may exert its therapeutic effects in CKD by modulating the TNF signaling pathway.
• Inhibition of the TNF pathway by losartan reduces renal fibrosis.
• These findings provide novel insights into the mechanism of action of losartan in treating kidney disease.