Quercetin is able to alleviate TGF‑β‑induced fibrosis in renal tubular epithelial cells by suppressing miR‑21

Abstract

Patients with chronic kidney disease (CKD) are characterized by a gradual loss of kidney function over time. A number of studies have indicated that tubule interstitial fibrosis (TIF) is associated with the occurrence and development of CKD. The aim of the present study was to investigate the effect of quercetin treatment on the fibrosis of renal tubular epithelial cells and to determine whether the anti-fibrotic effects of quercetin are achieved via microRNA (miR)-21. Human tubular epithelial HK-2 cells were cultured with transforming growth factor (TGF)-β to induce fibrosis and the expression of fibrotic markers collagen I, fibronectin, α-smooth muscle actin (SMA) and epithelial-cadherin were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. Cells were treated with 7.5, 15 or 30 mg/ml quercetin, following which fibrosis and miR-21 expression were evaluated. Quercetin-treated cells were transfected with miR-21 mimics and the expression of fibrotic markers was examined using RT-qPCR. Finally, the expression of fibrosis-associated miR-21 target genes, phosphatase and tensin homolog (PTEN) and TIMP Metallopeptidase Inhibitor 3 (TIMP3), was measured in cells treated with quercetin with or without miR-21 mimics using RT-qPCR, western blotting and immunocytochemistry. The results revealed that TGF-β treatment induced a significant increase in the expression of fibrotic markers in HK-2 cells, while quercetin treatment partially inhibited the fibrosis of HK-2 cells. Furthermore, quercetin treatment significantly inhibited TGF-β-induced miR-21 upregulation and transfection with miR-21 mimics reversed the anti-fibrotic effects of quercetin. Quercetin treatment markedly upregulated PTEN and TIMP3 expression, whereas transfection with miR-21 mimics reversed this effect. The results of the present study suggest that quercetin is able to alleviate TGF-β-induced fibrosis in HK-2 cells via suppressing the miR-21 and upregulating PTEN and TIMP3. Quercetin may have potential as an anti-fibrotic treatment for patients with renal fibrosis.

Dasatinib plus quercetin prevents uterine age-related dysfunction and fibrosis in mice

“…Gao et al found that the cardiac anti-fibrotic effect of isorhamnetin, a quercetin methylated metabolite, occurs due to blockage of the Pi3k/Akt/mTor signaling pathway [48]. Cao et al found that quercetin is able to reduce the TGF-βinduced fibrotic process in human tubular epithelial HK-2 cells through miR-21 suppression and PTEN upregulation [49]. Zhang et al in an in vitro study of the imatinib-resistant chronic myeloid leukemia cell line K562 (K562R IMT ) demonstrated the inhibitory effect of dasatinib on the Pi3k/Akt/mTor signaling pathway and observed a slight upregulation of Pten at high doses of the drug [50].…”

Small molecule inhibitors of epithelial‐mesenchymal transition for the treatment of cancer and fibrosis

“…Both rhamnetin and cirsiliol induced radio‐senitization and inhibited EMT by miR‐34a/Notch1 signaling in non–small‐cell lung cancer cells . Quercetin alleviated TGF‐β1‐induced fibrosis in HK‐2 cells via downregulating miR‐21 expression and upregulating PTEN and TIMP metallopeptidase inhibitor 3 (TIMP3) expression . Sophocarpine from Sophora alopecuroides L. inhibited tumor progression and reversed EMT by targeting miR‐21 in head and neck cancer .…”

“…40 Quercetin alleviated TGF-β1-induced fibrosis in HK-2 cells via downregulating miR-21 expression and upregulating PTEN and TIMP metallopeptidase inhibitor 3 (TIMP3) expression. 45 Sophocarpine from Sophora alopecuroides L. inhibited tumor progression and reversed EMT by targeting miR-21 in head and neck cancer. 51 In addition, sophocarpine exerted a profound antitumor effect through inhibiting EMT induced by TGF-β.…”

The effect of quercetin on microRNA expression: A critical review

“…Several miRNA molecules were expressed with a common pattern among in vitro and in vivo experiments as a result of quercetin treatment. miR-21 in particular was deregulated in the same manner (downregulation) in MCF-7, BEAS-2B and HK-2 cell lines and in two in vivo models (mouse/ rat) [67][68][69]81 . The literature search identified a few exceptions in two articles that reported quercetin mediated upregulation of miR-21 in the majority of samples 65,84 .…”

“…In addition, important information is missing in the paper, e.g. duration of incubation during selected experiments 69 .…”