Naringin attenuates renal interstitial fibrosis by regulating the TGF‑β/Smad signaling pathway and inflammation

Abstract

Interstitial fibrosis is a typical feature of all progres- sive renal diseases. The process of fibrosis is frequently coupled with the presence of pro-fibrotic factors and inflam- mation. Naringin is a dihydroflavone compound that has been previously reported to exhibit anti-fibrotic effects in the liver, where it prevents oxidative damage. In the present study, a rat model of renal interstitial fibrosis and fibrosis cell model were established to evaluate the effects of naringin on inflammatory proteins and fibrosis markers in kidney of rats and NRK-52E cells, and to elucidate the role of the TGF-beta/Smad signaling pathway in this mechanism. Compared with those in fibrotic NRK-52E cells that were stimulated by transforming growth factor-beta (TGF-beta), gene expression levels of alpha-smooth muscle actin (alpha-SMA), collagen 1 (COL1A1), collagen 3 (COL3A1), interleukin (IL)-1beta, IL-6 and tumor necrosis factor-alpha (TNF-alpha) were all found to be significantly decreased in fibrotic NRK-52E cells following treatment with naringin (50, 100 and 200 ng/ml). Results from the histopathological studies showed that naringin treatment preserved the renal tissue structure and reduced the degree of fibrosis in the kidney tissues of rats that underwent unilateral ureteral obstruction (UUO). In addition, naringin administration reduced the expression of alpha-SMA, COL1A1, COL3A1, IL-1beta, IL-6 and TNF-alpha in the kidneys of rats following UUO. The current study, using western blot analysis, indicated that naringin also downregu- lated the activation of Smad2/3 and the expression of Smad4, high-mobility group protein B1, activator protein-1, NF-kappaB and cyclooxygenase-2 whilst upregulating the expression of Smad7 in fibrotic NRK-52E cells and rats in the UUO group. In conclusion, naringin could antagonize renal interstitial fibrosis by regulating the TGF-beta/Smad pathway and the expression of inflammatory factors.