Renal CD14 expression correlates with the progression of cystic kidney disease

• Type of Material: Article
• Authors: Juling Zhou, University of Alabama; Xiaosen Ouyang, University of Alabama; Xiangqin Cui, Emory University; Trenton R. Schoeb, University of Alabama Birmingham; Lesley E. Smythies, University of Alabama Birmingham; Martin R. Johnson, University of Alabama Birmingham; Lisa M. Guay-Woodford, University of Alabama Birmingham; Arlene Chapman, Emory University; Michal Mrug, University of Alabama Birmingham
• Language: English
• Date: 2010-09-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2010 International Society of Nephrology.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/ki.2010.175
• Title of Journal or Parent Work: Kidney International
• ISSN: 0085-2538
• Volume: 78
• Issue: 6
• Start Page: 550
• End Page: 560
• Grant/Funding Information: Dr. Cui was supported in part by the UAB-UCSD O’Brien Center 1P30 DK079337.; Histology services were provided by the UAB Animal Resources Program Comparative Pathology Laboratory.; This work was supported in part by the Polycystic Kidney Disease Foundation Grant-In-Aid (M.M.), Pilot and Feasibility study from UAB Recessive PKD Core Center P30 DK074038 (M.M), American Heart Association National Scientist Development Grant (MM), UAB Digestive Disease Research Development Center DK064400 (LES) and AI083539 (LES).
• Keywords: GENE; MODEL; biomarkers; Life Sciences & Biomedicine; SOLUBLE CD14; AUTOSOMAL-DOMINANT; CD14; MONOCYTE CHEMOATTRACTANT PROTEIN-1; OVEREXPRESSION; Science & Technology; ENCODES; polycystic kidney disease; TOLL-LIKE RECEPTOR; PATHWAY; Urology & Nephrology; cpk mouse; EPITHELIAL-CELLS; innate immune response
• Research Categories: Health Sciences, Pathology; Biology, Genetics; Health Sciences, Medicine and Surgery

Abstract

Monocyte and macrophage markers are among the most highly overexpressed genes in cpk mouse kidneys with severely progressive renal cystic disease. We show here that one of these markers, CD14, is abnormally transcribed, activated and shed in cystic kidneys. However, these abnormalities were not associated with an increased number of interstitial CD14-positive mononuclear cells. Instead, we found that most non-cystic and cystic renal tubular epithelia were CD14-positive; even distal nephron-derived principal cells. Cd14 was significantly overexpressed in the kidneys of 5-day-old cpk mice and further increased as the disease progressed. In the cpk model with variable rates of cystic kidney enlargement (due to an intercross of two distinct genetic backgrounds), Cd14 expression positively correlated with kidney volume, exceeding the correlation with MCP-1, an established marker of autosomal-dominant polycystic kidney disease (ADPKD). In 16 patients with ADPKD, the baseline urinary CD14 level showed some tendency to correlate with the 2-year change in total kidney volume; however, the tendency was not statistically significant. But the association was significant when the analysis was confined to males. Clearly more studies need to be done to evaluate the utility of CD14 as a marker for outcomes in ADPKD.