Losartan ameliorates renal interstitial fibrosis through metabolic pathway and Smurfs-TGF-β/Smad

The genesis and development of renal fibrosis involve a variety of pathways closely related to inflammation, cytokines, oxidative stress and metabolic abnormalities. Renal fibrosis is the result of a complex combination of a variety of lesions. Epithelial-mesenchymal transdifferentiation (EMT) of renal tubular epithelial cells is considered the key to renal fibrosis. Losartan is a typical Angiotensin II (ANG II) receptor antagonist and relaxes blood vessels. In this study, we investigated the effects of losartan on Unilateral Ureteral Obstruction (UUO) model mice by studying the changes in the TGF-beta/Smad and metabolomics. Male C57BL/6 J mice were intervened with the UUO model and given losartan (10, 20, 30 mg/kg/d) for 28 consecutive days. The results showed that losartan could reduce UUO-induced abnormal serum metabolic spectrum and renal function. It could also improve renal tubular-interstitial injury and fibrosis by reducing tubulointerstitial dilation and collagen deposition. In addition, losartan promoted the expression of Smurf2 and Smurf1, i.e., Smad7 and E3 ubiquitin-linked enzymes, in the nucleus to degrade the type I receptor of TGF-beta 1 (T beta R-I) and P-Smad2/3 to inhibit renal tubular epithelial cells EMT. In summary, these findings indicated that losartan could regulate the TGF-beta/Smad and metabolic pathway in UUO model mice through ubiquitination to reduce renal fibrosis.

Automated summary

The genesis and development of renal fibrosis involve various pathways related to inflammation, cytokines, oxidative stress, and metabolic abnormalities. Losartan, as a medication, can reduce renal fibrosis by regulating the TGF-beta/Smad and metabolic pathways.