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

Abstract

Interstitial fibrosis is a typical feature of all progressive renal diseases. The process of fibrosis is frequently coupled with the presence of pro-fibrotic factors and inflammation. 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-β/Smad signaling pathway in this mechanism. Compared with those in fibrotic NRK-52E cells that were stimulated by transforming growth factor-β (TGF-β), gene expression levels of α-smooth muscle actin (α-SMA), collagen 1 (COL1A1), collagen 3 (COL3A1), interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) 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 α-SMA, COL1A1, COL3A1, IL-1β, IL-6 and TNF-α in the kidneys of rats following UUO. The current study, using western blot analysis, indicated that naringin also downregulated the activation of Smad2/3 and the expression of Smad4, high-mobility group protein B1, activator protein-1, NF-κB 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-β/Smad pathway and the expression of inflammatory factors.

Renal Interstitial Cells Promote Nephron Regeneration by Secreting Prostaglandin E2

“…Interestingly, we found a new cell type (cluster 12). These cells expressed well-known markers of interstitial cells, including collagen type 1 alpha 1b ( col1a1b ), collagen type 1 alpha 2 ( col1a2 ), collagen type 6 alpha 4a ( col6a4a ), and matrix metallopeptidase 2 ( mmp2 ) (Fitzgerald, Rich, Zhou, & Hansen, 2008; Guo et al, 2020; Kallakury et al, 2001; Wang et al, 2021) ( Figure 1B and Figure 1 — figure supplement 1A-D ). We speculate that this (Her, Chiang, Chen, & Wu, 2003) cell type was RICs.…”

Network Pharmacology and Experimental Assessment to Explore the Pharmacological Mechanism of Qimai Feiluoping Decoction Against Pulmonary Fibrosis

“…First, the PubChem database was used to obtain the molecular structure files of the 43 QM components. The potential therapeutic targets of the 43 ingredients were obtained from the PharmaMapper database, the ChemMapper database, the SwissTarget database, and the literature reports ( Bunbupha et al, 2020 ; He et al, 2020a ; Wang et al, 2021 ). These targets were screened according to many parameters, such as fit score ≥3.0 in the PharmaMapper database, score ≥0.4 in the ChemMapper database, and probability ≥0.4 in the SwissTarget database.…”

Effects of cytokine signaling inhibition on inflammation-driven tissue remodeling

“…Wang et al. explored the effects of the dihydroflavonoid naringin on TGF-β-induced fibrotic renal epithelial cells ( Wang et al., 2021 ). Cell fibrosis, characterized by the expression of α-SMA, was decreased following treatment with naringin, highlighting its ability to inhibit the fibrotic effect of TGF-β.…”

“…Treatment with naringin significantly reduced all fibrotic markers both in vivo and in vitro, highlighting its effectiveness as an anti-fibrotic drug. Naringin moreover improved the atrophy of kidney tubular cells following fibrotic injury, which suggests that it may have a clinically useful effect ( Wang et al., 2021 ).…”