Year-end Sale % OFF 
Abstract
Kidney fibrosis has been accepted to be a common pathological outcome of chronic kidney disease (CKD). We aimed to examine serum levels and tissue expression of chemokine (C-C motif) ligand 8 (CCL8) in patients with CKD and to investigate their association with kidney fibrosis in CKD model. Serum levels and tissue expression of CCL8 significantly increased with advancing CKD stage, proteinuria level, and pathologic deterioration. In Western blot analysis of primary cultured human tubular epithelial cells after induction of fibrosis with rTGF-β, CCL8 was upregulated by rTGF-β treatment and the simultaneous treatment with anti-CCL8 mAb mitigated the rTGF-β-induced an increase in fibronectin and a decrease E-cadherin and BCL-2 protein levels. The antiapoptotic effect of the anti-CCL8 mAb was also demonstrated by Annexin V/propidium iodide staining assay. In qRT-PCR analysis, mRNA expression levels of the markers for fibrosis and apoptosis showed similar expression patterns to those observed by western blotting. The immunohistochemical analysis revealed CCL8 and fibrosis- and apoptosis-related markers significantly increased in the unilateral ureteral obstruction model, which agrees with our in vitro findings. In conclusion, CCL8 pathway is associated with increased risk of kidney fibrosis and that CCL8 blockade can ameliorate kidney fibrosis and apoptosis.
Highlights
Chronic kidney disease (CKD) is a major concern associated with high mortality and morbidity [1]
We further investigated the tissue expression of CCR2, which is a known counterpart of CCL8
These results indicated that Transforming growth factor-β (TGF-β) induced fibrosis in Human tubular epithelial cells (hTECs) via the upregulation of CCL8
Summary
Chronic kidney disease (CKD) is a major concern associated with high mortality and morbidity [1]. The final common pathway in this process has been thoroughly investigated, and kidney fibrosis, which is characterized by a serial process of tubulointerstitial fibrosis, tubular atrophy, and glomerulosclerosis, has been accepted as a common pathological outcome of CKD, regardless of etiology [3–10]. During this process, hypoxia plays a pathogenic role in the relatively early stages of CKD, before the development of structural tubulointerstitial injury [2,11]. Transforming growth factor-β (TGF-β) has been reported as a key factor in regulating kidney fibrosis [9]. TGF-β can promote epithelial-to-mesenchymal transition (EMT) to become myofibroblasts of tubular epithelial cells (TECs) and alter the extracellular matrix metabolism of resident kidney cells [14–16]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
