Total flavonoids from Smilax glabra Roxb blocks epithelial‐mesenchymal transition and inhibits renal interstitial fibrosis by targeting miR‐21/PTEN signaling. Issue 3 (10th October 2018)

• Record Type: Journal Article
• Authors: Luo, Qihan; Cai, Zhaowei; Tu, Jue; Ling, Yun; Wang, Dejun; Cai, Yueqin
• Is Part Of: Journal of cellular biochemistry. Volume 120:Issue 3(2019)
• Page Start: 3861
• Page End: 3873
• Publication Date: 2018-10-10
• Subjects: epithelial‐mesenchymal transition -- microRNA‐21 -- pure total flavonoids from Smilax glabra Roxb -- renal interstitial fibrosis -- unilateral ureteral obstruction; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.27668
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: Background: Smilax glabra Roxb, a traditional Chinese herb, has been widely used in folk medicine. The current study was performed to investigate the protective effect of S. glabra Roxb extract, pure total flavonoids from Smilax glabra Roxb (PTFS), on renal interstitial fibrosis (RIF) and its underlying mechanism. Methods: First, a surgical model of unilateral ureteral obstruction was established in rats to induce RIF. Then, rats were grouped and treated with PTFS at different concentration. Second, HK‐2 cells underwent an epithelial‐mesenchymal transition (EMT) by the addition of transforming growth factor‐β1 (TGF‐β1). Additionally, HK‐2 cells after inducing for EMT were transfected with microRNA‐21 (miR‐21) mimic or inhibitor. These HK‐2 cells were grouped and treated with PTFS at different concentration. Finally, real‐time polymerase chain reaction and Western blot analysis were performed to detect the expression of possible signaling factor involved in RIF in renal tissues or HK‐2 cells after PTFS treatment. Results: In vivo and in vitro experiments indicated that PTFS treatment could decrease the expression of α‐smooth muscle actin (α‐SMA; mesenchymal marker) and increase the expression of E‐cadherin (epithelial marker) in both messenger RNA and protein level. Moreover, PTFS also attenuated the expression of TGF‐β1/Smad signaling in both renal tissues and HK‐2 cells that underwent EMT. Overexpression or inhibition of miR‐21 in HK‐2 cells activated or blocked the PI3K/Akt signaling via targeting phosphatase and tension homolog (PTEN), and then promoted or suppressed the progress of TGF‐β1‐induced EMT by regulating the expression of α‐SMA and E‐cadherin. Furthermore, PTFS treatment inhibited TGF‐β1‐induced EMT progress by blocking miR‐21/PTEN/PI3K/Akt signaling. Conclusion: PTFS has strong anti‐EMT and antifibrosis effects both in vitro and in vivo. The mechanism underlying these effects may be related to inhibition of TGF‐β1/Smad, and their downstream miR‐21/PTEN signaling, leading to blocks of EMT process during RIF. Abstract : Pure total flavonoids from Smilax glabra Roxb (PTFS) has strong anti‐epithelial‐mesenchymal transition (EMT) and antifibrosis effects both in vitro and in vivo. The mechanism underlying these effects may be related to inhibition of transforming growth factor‐β1 (TGF‐β1)/Smad, and their downstream microRNA‐21/phosphatase and tension homolog (PTEN) signaling, leading to blocks of EMT process during renal interstitial fibrosis. α‐SMA, α‐smooth muscle actin