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C-C Motif Chemokine Ligand-17 as a Novel Biomarker and Regulator of Epithelial Mesenchymal Transition in Renal Fibrogenesis

CCL17, a chemotactic cytokine produced by macrophages, is known to promote inflammatory and fibrotic effects in multiple organs, but its role in mediating renal fibrosis is unclear. In our study cohort of 234 chronic kidney disease (CKD) patients and 65 healthy controls, human cytokine array analysi...

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Autores principales: Hsieh, Yi-Hsien, Wang, Wen-Chien, Hung, Tung-Wei, Lee, Chu-Che, Tsai, Jen-Pi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699042/
https://www.ncbi.nlm.nih.gov/pubmed/34943853
http://dx.doi.org/10.3390/cells10123345
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author Hsieh, Yi-Hsien
Wang, Wen-Chien
Hung, Tung-Wei
Lee, Chu-Che
Tsai, Jen-Pi
author_facet Hsieh, Yi-Hsien
Wang, Wen-Chien
Hung, Tung-Wei
Lee, Chu-Che
Tsai, Jen-Pi
author_sort Hsieh, Yi-Hsien
collection PubMed
description CCL17, a chemotactic cytokine produced by macrophages, is known to promote inflammatory and fibrotic effects in multiple organs, but its role in mediating renal fibrosis is unclear. In our study cohort of 234 chronic kidney disease (CKD) patients and 65 healthy controls, human cytokine array analysis revealed elevated CCL17 expression in CKD that correlated negatively with renal function. The area under the receiver operating characteristic curve of CCL17 to predict the development of CKD stages 3b–5 was 0.644 (p < 0.001), with the optimal cut-off value of 415.3 ng/mL. In vitro over-expression of CCL17 in HK2 cells had no effect on cell viability, but increased cell motility and the expression of α-SMA, vimentin and collagen I, as shown by western blot analysis. In a unilateral ureteral obstruction (UUO) mouse model, we observed significantly increased interstitial fibrosis and renal tubule dilatation by Masson’s Trichrome and H&E staining, and markedly increased expression of CCL17, vimentin, collagen I, and α-SMA by IHC stain, qRTPCR, and western blotting. CCL17 induced renal fibrosis by promoting the epithelial-mesenchymal transition, resulting in ECM accumulation. CCL17 may be a useful biomarker for predicting the development of advanced CKD.
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spelling pubmed-86990422021-12-24 C-C Motif Chemokine Ligand-17 as a Novel Biomarker and Regulator of Epithelial Mesenchymal Transition in Renal Fibrogenesis Hsieh, Yi-Hsien Wang, Wen-Chien Hung, Tung-Wei Lee, Chu-Che Tsai, Jen-Pi Cells Article CCL17, a chemotactic cytokine produced by macrophages, is known to promote inflammatory and fibrotic effects in multiple organs, but its role in mediating renal fibrosis is unclear. In our study cohort of 234 chronic kidney disease (CKD) patients and 65 healthy controls, human cytokine array analysis revealed elevated CCL17 expression in CKD that correlated negatively with renal function. The area under the receiver operating characteristic curve of CCL17 to predict the development of CKD stages 3b–5 was 0.644 (p < 0.001), with the optimal cut-off value of 415.3 ng/mL. In vitro over-expression of CCL17 in HK2 cells had no effect on cell viability, but increased cell motility and the expression of α-SMA, vimentin and collagen I, as shown by western blot analysis. In a unilateral ureteral obstruction (UUO) mouse model, we observed significantly increased interstitial fibrosis and renal tubule dilatation by Masson’s Trichrome and H&E staining, and markedly increased expression of CCL17, vimentin, collagen I, and α-SMA by IHC stain, qRTPCR, and western blotting. CCL17 induced renal fibrosis by promoting the epithelial-mesenchymal transition, resulting in ECM accumulation. CCL17 may be a useful biomarker for predicting the development of advanced CKD. MDPI 2021-11-29 /pmc/articles/PMC8699042/ /pubmed/34943853 http://dx.doi.org/10.3390/cells10123345 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hsieh, Yi-Hsien
Wang, Wen-Chien
Hung, Tung-Wei
Lee, Chu-Che
Tsai, Jen-Pi
C-C Motif Chemokine Ligand-17 as a Novel Biomarker and Regulator of Epithelial Mesenchymal Transition in Renal Fibrogenesis
title C-C Motif Chemokine Ligand-17 as a Novel Biomarker and Regulator of Epithelial Mesenchymal Transition in Renal Fibrogenesis
title_full C-C Motif Chemokine Ligand-17 as a Novel Biomarker and Regulator of Epithelial Mesenchymal Transition in Renal Fibrogenesis
title_fullStr C-C Motif Chemokine Ligand-17 as a Novel Biomarker and Regulator of Epithelial Mesenchymal Transition in Renal Fibrogenesis
title_full_unstemmed C-C Motif Chemokine Ligand-17 as a Novel Biomarker and Regulator of Epithelial Mesenchymal Transition in Renal Fibrogenesis
title_short C-C Motif Chemokine Ligand-17 as a Novel Biomarker and Regulator of Epithelial Mesenchymal Transition in Renal Fibrogenesis
title_sort c-c motif chemokine ligand-17 as a novel biomarker and regulator of epithelial mesenchymal transition in renal fibrogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699042/
https://www.ncbi.nlm.nih.gov/pubmed/34943853
http://dx.doi.org/10.3390/cells10123345
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