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Total flavonoids from Smilax glabra Roxb blocks epithelial-mesenchymal transition and inhibits renal interstitial fibrosis by targeting miR-21/PTEN signaling.
J Cell Biochem. 2019 03; 120(3):3861-3873.JC

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.

Authors+Show Affiliations

Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China. College of Pharmacy, Zhejiang Chinese Medical University, Hangzhou 310053, China.Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30304552

Citation

Luo, Qihan, et al. "Total Flavonoids From Smilax Glabra Roxb Blocks Epithelial-mesenchymal Transition and Inhibits Renal Interstitial Fibrosis By Targeting miR-21/PTEN Signaling." Journal of Cellular Biochemistry, vol. 120, no. 3, 2019, pp. 3861-3873.
Luo Q, Cai Z, Tu J, et al. Total flavonoids from Smilax glabra Roxb blocks epithelial-mesenchymal transition and inhibits renal interstitial fibrosis by targeting miR-21/PTEN signaling. J Cell Biochem. 2019;120(3):3861-3873.
Luo, Q., Cai, Z., Tu, J., Ling, Y., Wang, D., & Cai, Y. (2019). Total flavonoids from Smilax glabra Roxb blocks epithelial-mesenchymal transition and inhibits renal interstitial fibrosis by targeting miR-21/PTEN signaling. Journal of Cellular Biochemistry, 120(3), 3861-3873. https://doi.org/10.1002/jcb.27668
Luo Q, et al. Total Flavonoids From Smilax Glabra Roxb Blocks Epithelial-mesenchymal Transition and Inhibits Renal Interstitial Fibrosis By Targeting miR-21/PTEN Signaling. J Cell Biochem. 2019;120(3):3861-3873. PubMed PMID: 30304552.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Total flavonoids from Smilax glabra Roxb blocks epithelial-mesenchymal transition and inhibits renal interstitial fibrosis by targeting miR-21/PTEN signaling. AU - Luo,Qihan, AU - Cai,Zhaowei, AU - Tu,Jue, AU - Ling,Yun, AU - Wang,Dejun, AU - Cai,Yueqin, Y1 - 2018/10/10/ PY - 2018/07/13/received PY - 2018/08/21/accepted PY - 2018/10/12/pubmed PY - 2020/6/20/medline PY - 2018/10/11/entrez KW - epithelial-mesenchymal transition KW - microRNA-21 KW - pure total flavonoids from Smilax glabra Roxb KW - renal interstitial fibrosis KW - unilateral ureteral obstruction SP - 3861 EP - 3873 JF - Journal of cellular biochemistry JO - J Cell Biochem VL - 120 IS - 3 N2 - 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. SN - 1097-4644 UR - https://www.unboundmedicine.com/medline/citation/30304552/Total_flavonoids_from_Smilax_glabra_Roxb_blocks_epithelial_mesenchymal_transition_and_inhibits_renal_interstitial_fibrosis_by_targeting_miR_21/PTEN_signaling_ L2 - https://doi.org/10.1002/jcb.27668 DB - PRIME DP - Unbound Medicine ER -