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

Abstract

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.

• Authors: Yi-Hsien Hsieh, Wen-Chien Wang, Tung-Wei Hung, Chu-Che Lee, Jen-Pi Tsai
• Journal: Cells (Cells) Vol. 10 Issue 12 (11 29 2021) ISSN: 2073-4409 [Electronic] Switzerland
• PMID: 34943853 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• CCL17 protein, human
• Chemokine CCL17
• RNA, Messenger

Topics

• Biomarkers (metabolism)
• Case-Control Studies
• Cell Cycle
• Cell Movement (genetics)
• Cell Survival (genetics)
• Chemokine CCL17 (genetics, metabolism)
• Epithelial-Mesenchymal Transition (genetics)
• Fibrosis
• Glomerular Filtration Rate
• Humans
• Kidney (metabolism, pathology, physiopathology)
• Models, Biological
• RNA, Messenger (genetics, metabolism)
• Renal Insufficiency, Chronic (genetics, pathology, physiopathology)
• Up-Regulation (genetics)
• Ureteral Obstruction (genetics, pathology)