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Role of transforming growth factor-beta1 in cyclosporine-induced epithelial-to-mesenchymal transition in gingival epithelium.
J Periodontol. 2015 Jan; 86(1):120-8.JP

Abstract

BACKGROUND

It has been proposed that cyclosporin A (CsA) may induce epithelial-to-mesenchymal transition (EMT) in gingiva. The aims of the present study are to confirm the notion that EMT occurs in human gingival epithelial (hGE) cells after CsA treatment and to investigate the role of transforming growth factor beta1 (TGF-β1) on this CsA-induced EMT.

METHODS

The effects of CsA, with and without TGF-β1 inhibitor, on the morphologic changes of primary culture of hGE cells were examined in vitro. The changes of protein and messenger RNA (mRNA) expressions of two EMT markers (E-cadherin and alpha-smooth muscle actin) in the hGE cells after CsA treatment with and without TGF-β1 inhibitor were evaluated with immunocytochemistry and real-time polymerase chain reaction.

RESULTS

The epithelial cells became spindle-like, elongated, and disassociated from neighboring cells and lost their original cobblestone monolayer pattern when CsA was added. However, the epithelial cells stayed in their original cobblestone morphology with treatment of TGF-β1 inhibitor on top of the CsA treatment. When CsA was given, the protein and mRNA expressions of E-cadherin and α-SMA were significantly altered, and these alterations were significantly reversed with pretreatment of TGF-β1 inhibitor.

CONCLUSIONS

CsA could induce Type 2 EMT in gingiva by changing the morphology of epithelial cells and altering the EMT markers/effectors. The CsA-induced gingival EMT is dependent or at least partially dependent on TGF-β1.

Authors+Show Affiliations

Department of Periodontology, School of Dentistry, National Defense Medical Center and Tri-Service General Hospital, Taipei, Taiwan, ROC.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

25272978

Citation

Fu, Martin M., et al. "Role of Transforming Growth Factor-beta1 in Cyclosporine-induced Epithelial-to-mesenchymal Transition in Gingival Epithelium." Journal of Periodontology, vol. 86, no. 1, 2015, pp. 120-8.
Fu MM, Chin YT, Fu E, et al. Role of transforming growth factor-beta1 in cyclosporine-induced epithelial-to-mesenchymal transition in gingival epithelium. J Periodontol. 2015;86(1):120-8.
Fu, M. M., Chin, Y. T., Fu, E., Chiu, H. C., Wang, L. Y., Chiang, C. Y., & Tu, H. P. (2015). Role of transforming growth factor-beta1 in cyclosporine-induced epithelial-to-mesenchymal transition in gingival epithelium. Journal of Periodontology, 86(1), 120-8. https://doi.org/10.1902/jop.2014.130285
Fu MM, et al. Role of Transforming Growth Factor-beta1 in Cyclosporine-induced Epithelial-to-mesenchymal Transition in Gingival Epithelium. J Periodontol. 2015;86(1):120-8. PubMed PMID: 25272978.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of transforming growth factor-beta1 in cyclosporine-induced epithelial-to-mesenchymal transition in gingival epithelium. AU - Fu,Martin M, AU - Chin,Yu-Tang, AU - Fu,Earl, AU - Chiu,Hsien-Chung, AU - Wang,Li-Yu, AU - Chiang,Cheng-Yang, AU - Tu,Hsiao-Pei, PY - 2014/10/3/entrez PY - 2014/10/3/pubmed PY - 2016/3/24/medline KW - Alpha-smooth muscle actin KW - cadherins KW - cyclosporine KW - epithelial-mesenchymal transition KW - gingiva KW - smad2 protein KW - smad3 protein KW - transforming growth factor beta1 SP - 120 EP - 8 JF - Journal of periodontology JO - J Periodontol VL - 86 IS - 1 N2 - BACKGROUND: It has been proposed that cyclosporin A (CsA) may induce epithelial-to-mesenchymal transition (EMT) in gingiva. The aims of the present study are to confirm the notion that EMT occurs in human gingival epithelial (hGE) cells after CsA treatment and to investigate the role of transforming growth factor beta1 (TGF-β1) on this CsA-induced EMT. METHODS: The effects of CsA, with and without TGF-β1 inhibitor, on the morphologic changes of primary culture of hGE cells were examined in vitro. The changes of protein and messenger RNA (mRNA) expressions of two EMT markers (E-cadherin and alpha-smooth muscle actin) in the hGE cells after CsA treatment with and without TGF-β1 inhibitor were evaluated with immunocytochemistry and real-time polymerase chain reaction. RESULTS: The epithelial cells became spindle-like, elongated, and disassociated from neighboring cells and lost their original cobblestone monolayer pattern when CsA was added. However, the epithelial cells stayed in their original cobblestone morphology with treatment of TGF-β1 inhibitor on top of the CsA treatment. When CsA was given, the protein and mRNA expressions of E-cadherin and α-SMA were significantly altered, and these alterations were significantly reversed with pretreatment of TGF-β1 inhibitor. CONCLUSIONS: CsA could induce Type 2 EMT in gingiva by changing the morphology of epithelial cells and altering the EMT markers/effectors. The CsA-induced gingival EMT is dependent or at least partially dependent on TGF-β1. SN - 1943-3670 UR - https://www.unboundmedicine.com/medline/citation/25272978/Role_of_transforming_growth_factor_beta1_in_cyclosporine_induced_epithelial_to_mesenchymal_transition_in_gingival_epithelium_ L2 - https://doi.org/10.1902/jop.2014.130285 DB - PRIME DP - Unbound Medicine ER -