Tags

Type your tag names separated by a space and hit enter

Suppression of CIP4/Par6 attenuates TGF-β1-induced epithelial-mesenchymal transition in NRK-52E cells.
Int J Mol Med. 2017 Oct; 40(4):1165-1171.IJ

Abstract

Transforming growth factor-β (TGF-β) induces epithelial-mesenchymal transition (EMT) primarily via a Smad‑dependent mechanism. However, there are few studies available on TGF-β-induced EMT through the activation of non‑canonical pathways. In this study, the Cdc42-interacting protein-4 (CIP4)/partitioning-defective protein 6 (Par6) pathway was investigated in TGF-β1‑stimulated NRK-52E cells. Rat NRK-52E cells were obtained and stimulated with TGF-β1. The expression levels of E-cadherin, α-smooth muscle actin (α-SMA) and CIP4 were then examined by western blot analyses. Rat NRK-52E cells were transfected with Par6 or CIP4 small interfering RNA (siRNA), and scrambled siRNA as controls. The cells were incubated with 20 ng/ml of TGF-β1 for 72 h in order to observe the effects of Par6 and CIP4 silencing. Confocal fluorescence microscopy was also applied to reveal the expression and distribution of E-cadherin, α-SMA, Par6 and CIP4. The results demonstrated that E-cadherin expression was decreased, and α-SMA expression was increased in the TGF-β1‑stimulated cells. Simultaneously, the increased expression of CIP4 and p-Par6 was confirmed by western blot analyses. The results of confocal fluorescence microscopy revealed that rat CIP4 exhibited cluster formations located adjacent to the cell periphery; however, as for the protein expression and distribution of Par6, there was no obvious difference between the control cells and cells exposed to TGF-β1. siRNA molecules capable of CIP4 and Par6 knockdown were used to demonstrate reversed TGF-β1‑induced EMT. Moreover, CIP4 loss of function reversed the increase in p-Par6 protein expression in the TGF-β1‑stimulated NRK-52E cells. A similar result was observed with the decreased CIP4 protein expression due to Par6 loss of function. Our data thus suggest that the CIP4/Par6 complex plays an important role in the occurrence of EMT in TGF-β1-stimulated NRK-52E cells. The underlying mechanisms are mediated, at least in part, through the upregulation of CIP4, which occurrs due to stimulation with TGF-β1; subsequently, CIP4 increases the phosphorylation of Par6, which accelerates the process of EMT.

Authors+Show Affiliations

Zhongshan Hospital Qingpu Branch, Fudan University, Shanghai 201700, P.R. China.Zhongshan Hospital Qingpu Branch, Fudan University, Shanghai 201700, P.R. China.Zhongshan Hospital Qingpu Branch, Fudan University, Shanghai 201700, P.R. China.Zhongshan Hospital Qingpu Branch, Fudan University, Shanghai 201700, P.R. China.Zhongshan Hospital Qingpu Branch, Fudan University, Shanghai 201700, P.R. China.Zhongshan Hospital Qingpu Branch, Fudan University, Shanghai 201700, P.R. China.Zhongshan Hospital Qingpu Branch, Fudan University, Shanghai 201700, P.R. China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28848997

Citation

Zhu, Ying-Chun, et al. "Suppression of CIP4/Par6 Attenuates TGF-β1-induced Epithelial-mesenchymal Transition in NRK-52E Cells." International Journal of Molecular Medicine, vol. 40, no. 4, 2017, pp. 1165-1171.
Zhu YC, Wang YK, Bai SJ, et al. Suppression of CIP4/Par6 attenuates TGF-β1-induced epithelial-mesenchymal transition in NRK-52E cells. Int J Mol Med. 2017;40(4):1165-1171.
Zhu, Y. C., Wang, Y. K., Bai, S. J., Zha, F. F., Feng, G., Gao, C. P., & Liu, J. (2017). Suppression of CIP4/Par6 attenuates TGF-β1-induced epithelial-mesenchymal transition in NRK-52E cells. International Journal of Molecular Medicine, 40(4), 1165-1171. https://doi.org/10.3892/ijmm.2017.3100
Zhu YC, et al. Suppression of CIP4/Par6 Attenuates TGF-β1-induced Epithelial-mesenchymal Transition in NRK-52E Cells. Int J Mol Med. 2017;40(4):1165-1171. PubMed PMID: 28848997.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Suppression of CIP4/Par6 attenuates TGF-β1-induced epithelial-mesenchymal transition in NRK-52E cells. AU - Zhu,Ying-Chun, AU - Wang,Ya-Kun, AU - Bai,Shou-Jun, AU - Zha,Fang-Fang, AU - Feng,Gang, AU - Gao,Cong-Pu, AU - Liu,Juan, Y1 - 2017/08/16/ PY - 2016/03/08/received PY - 2017/08/01/accepted PY - 2017/8/30/pubmed PY - 2018/5/16/medline PY - 2017/8/30/entrez SP - 1165 EP - 1171 JF - International journal of molecular medicine JO - Int. J. Mol. Med. VL - 40 IS - 4 N2 - Transforming growth factor-β (TGF-β) induces epithelial-mesenchymal transition (EMT) primarily via a Smad‑dependent mechanism. However, there are few studies available on TGF-β-induced EMT through the activation of non‑canonical pathways. In this study, the Cdc42-interacting protein-4 (CIP4)/partitioning-defective protein 6 (Par6) pathway was investigated in TGF-β1‑stimulated NRK-52E cells. Rat NRK-52E cells were obtained and stimulated with TGF-β1. The expression levels of E-cadherin, α-smooth muscle actin (α-SMA) and CIP4 were then examined by western blot analyses. Rat NRK-52E cells were transfected with Par6 or CIP4 small interfering RNA (siRNA), and scrambled siRNA as controls. The cells were incubated with 20 ng/ml of TGF-β1 for 72 h in order to observe the effects of Par6 and CIP4 silencing. Confocal fluorescence microscopy was also applied to reveal the expression and distribution of E-cadherin, α-SMA, Par6 and CIP4. The results demonstrated that E-cadherin expression was decreased, and α-SMA expression was increased in the TGF-β1‑stimulated cells. Simultaneously, the increased expression of CIP4 and p-Par6 was confirmed by western blot analyses. The results of confocal fluorescence microscopy revealed that rat CIP4 exhibited cluster formations located adjacent to the cell periphery; however, as for the protein expression and distribution of Par6, there was no obvious difference between the control cells and cells exposed to TGF-β1. siRNA molecules capable of CIP4 and Par6 knockdown were used to demonstrate reversed TGF-β1‑induced EMT. Moreover, CIP4 loss of function reversed the increase in p-Par6 protein expression in the TGF-β1‑stimulated NRK-52E cells. A similar result was observed with the decreased CIP4 protein expression due to Par6 loss of function. Our data thus suggest that the CIP4/Par6 complex plays an important role in the occurrence of EMT in TGF-β1-stimulated NRK-52E cells. The underlying mechanisms are mediated, at least in part, through the upregulation of CIP4, which occurrs due to stimulation with TGF-β1; subsequently, CIP4 increases the phosphorylation of Par6, which accelerates the process of EMT. SN - 1791-244X UR - https://www.unboundmedicine.com/medline/citation/28848997/Suppression_of_CIP4/Par6_attenuates_TGF_β1_induced_epithelial_mesenchymal_transition_in_NRK_52E_cells_ L2 - http://www.spandidos-publications.com/ijmm/40/4/1165 DB - PRIME DP - Unbound Medicine ER -