Tags

Type your tag names separated by a space and hit enter

Regulation of epithelial mesenchymal transition by the renin-angiotensin system: a role for klotho in renal tubular epithelial cells.
J Biol Regul Homeost Agents. 2020 Jan-Feb; 34(1):57-67.JB

Abstract

Klotho is a putative aging suppressor gene that is primarily expressed in renal tubular epithelial cells. Its expression has been reported to protect against fibrosis in human chronic kidney disease. However, the roles of klotho in epithelial-mesenchymal transition (EMT) and renal fibrosis are yet to be elucidated. The present study aimed to investigate the putative roles of klotho in angiotensin (Ang) II-induced damage of renal tubular epithelial cells. NRK-52E rat cells were treated with various combinations of Ang II, the Ang-converting enzyme inhibitor fosinopril (Fos) and the Ang II receptor antagonist valsartan (Val). The levels of transforming growth factor (TGF)-β1, soluble klotho, α-smooth muscle actin (α-SMA) and E-cadherin in NRK-52E culture supernatants were measured using enzyme-linked immunosorbent assays. Furthermore, the mRNA and protein expression of TGF-β1, klotho, α-SMA and E-cadherin was detected using semiquantitative reverse transcription-polymerase chain reaction, immunocytochemistry and Western blot analysis. The results demonstrated that Ang II inhibited the expression of klotho and E-cadherin, while it upregulated the expression of TGF-β1 and α-SMA, in NRK52E cells. Fos and/or Val were revealed to enhance klotho and E-cadherin expression, and suppress the expression of TGF-β1 and α-SMA, compared with the Ang II-only group. Furthermore, a positive linear correlation was detected between the expression of klotho and E-cadherin, while negative linear correlations with klotho expression were detected for TGF-β1 and α-SMA expression. In conclusion, the expression of klotho was demonstrated to be enhanced following treatment with Fos and Val in Ang II-treated NRK-52E cells. The present results indicate that klotho may be involved in the inhibition of Ang II-induced EMT in renal tubular epithelial cells. Therefore, klotho may serve as a protective factor in renal tubulointerstitial fibrosis and aid the treatment of chronic kidney disease (CKD) patients using precision therapy.

Authors+Show Affiliations

Department of Rheumatology, Hainan General Hospital, Haikou City, Hainan Province, China.Department of Rheumatology, Hainan General Hospital, Haikou City, Hainan Province, China.Department of Rheumatology, Hainan General Hospital, Haikou City, Hainan Province, China.Department of Rheumatology, Hainan General Hospital, Haikou City, Hainan Province, China.Department of Rheumatology, Hainan General Hospital, Haikou City, Hainan Province, China.Department of Rheumatology, Hainan General Hospital, Haikou City, Hainan Province, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32466632

Citation

Yang, Z, et al. "Regulation of Epithelial Mesenchymal Transition By the Renin-angiotensin System: a Role for Klotho in Renal Tubular Epithelial Cells." Journal of Biological Regulators and Homeostatic Agents, vol. 34, no. 1, 2020, pp. 57-67.
Yang Z, Zhan YW, Huang YY, et al. Regulation of epithelial mesenchymal transition by the renin-angiotensin system: a role for klotho in renal tubular epithelial cells. J Biol Regul Homeost Agents. 2020;34(1):57-67.
Yang, Z., Zhan, Y. W., Huang, Y. Y., Huang, W., Zhan, F., & Lin, S. D. (2020). Regulation of epithelial mesenchymal transition by the renin-angiotensin system: a role for klotho in renal tubular epithelial cells. Journal of Biological Regulators and Homeostatic Agents, 34(1), 57-67. https://doi.org/10.23812/19-410-A-27
Yang Z, et al. Regulation of Epithelial Mesenchymal Transition By the Renin-angiotensin System: a Role for Klotho in Renal Tubular Epithelial Cells. J Biol Regul Homeost Agents. 2020 Jan-Feb;34(1):57-67. PubMed PMID: 32466632.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of epithelial mesenchymal transition by the renin-angiotensin system: a role for klotho in renal tubular epithelial cells. AU - Yang,Z, AU - Zhan,Y W, AU - Huang,Y Y, AU - Huang,W, AU - Zhan,F, AU - Lin,S D, PY - 2020/5/30/entrez PY - 2020/5/30/pubmed PY - 2020/6/27/medline KW - angiotensin II KW - epithelial-mesenchymal transition KW - fosinopril KW - klotho KW - valsartan SP - 57 EP - 67 JF - Journal of biological regulators and homeostatic agents JO - J. Biol. Regul. Homeost. Agents VL - 34 IS - 1 N2 - Klotho is a putative aging suppressor gene that is primarily expressed in renal tubular epithelial cells. Its expression has been reported to protect against fibrosis in human chronic kidney disease. However, the roles of klotho in epithelial-mesenchymal transition (EMT) and renal fibrosis are yet to be elucidated. The present study aimed to investigate the putative roles of klotho in angiotensin (Ang) II-induced damage of renal tubular epithelial cells. NRK-52E rat cells were treated with various combinations of Ang II, the Ang-converting enzyme inhibitor fosinopril (Fos) and the Ang II receptor antagonist valsartan (Val). The levels of transforming growth factor (TGF)-β1, soluble klotho, α-smooth muscle actin (α-SMA) and E-cadherin in NRK-52E culture supernatants were measured using enzyme-linked immunosorbent assays. Furthermore, the mRNA and protein expression of TGF-β1, klotho, α-SMA and E-cadherin was detected using semiquantitative reverse transcription-polymerase chain reaction, immunocytochemistry and Western blot analysis. The results demonstrated that Ang II inhibited the expression of klotho and E-cadherin, while it upregulated the expression of TGF-β1 and α-SMA, in NRK52E cells. Fos and/or Val were revealed to enhance klotho and E-cadherin expression, and suppress the expression of TGF-β1 and α-SMA, compared with the Ang II-only group. Furthermore, a positive linear correlation was detected between the expression of klotho and E-cadherin, while negative linear correlations with klotho expression were detected for TGF-β1 and α-SMA expression. In conclusion, the expression of klotho was demonstrated to be enhanced following treatment with Fos and Val in Ang II-treated NRK-52E cells. The present results indicate that klotho may be involved in the inhibition of Ang II-induced EMT in renal tubular epithelial cells. Therefore, klotho may serve as a protective factor in renal tubulointerstitial fibrosis and aid the treatment of chronic kidney disease (CKD) patients using precision therapy. SN - 0393-974X UR - https://www.unboundmedicine.com/medline/citation/32466632/Regulation_of_epithelial_mesenchymal_transition_by_the_renin_angiotensin_system:_a_role_for_klotho_in_renal_tubular_epithelial_cells_ L2 - https://antibodies.cancer.gov/detail/CPTC-FOS-4 DB - PRIME DP - Unbound Medicine ER -