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Mediators of Inflammation
Volume 2016, Article ID 5802973, 10 pages
Research Article

Indoxyl Sulfate Induces Mesangial Cell Proliferation via the Induction of COX-2

1Department of Nephrology, Nanjing Children’s Hospital, Nanjing Medical University, Nanjing, China
2Institute of Pediatrics, Nanjing Medical University, Nanjing, China
3Nanjing Key Laboratory of Pediatrics, Nanjing Children’s Hospital, Nanjing Medical University, Nanjing, China

Received 10 August 2016; Accepted 27 September 2016

Academic Editor: Vinod K. Mishra

Copyright © 2016 Shuzhen Li et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Indoxyl sulfate (IS) is one of important uremic toxins and is markedly accumulated in the circulation of end stage renal disease (ESRD) patients, which might contribute to the damage of residual nephrons and progressive loss of residual renal function (RRF). Thus this study was undertaken to investigate the role of IS in modulating mesangial cell (MC) proliferation and the underlying mechanism. The proliferation of MCs induced by IS was determined by cell number counting, DNA synthase rate, and cell cycle phase analysis. COX-2 expression was examined by Western blotting and qRT-PCR, and a specific COX-2 inhibitor NS398 was applied to define its role in IS-induced MC proliferation. Following IS treatment, MCs exhibited increased total cell number, DNA synthesis rate, and number of cells in S and G2 phases paralleled with the upregulation of cyclin A2 and cyclin D1. Next, we found an inducible inflammation-related enzyme COX-2 was remarkably enhanced by IS, and the inhibition of COX-2 by NS398 significantly blocked IS-induced MC proliferation in line with a blockade of PGE2 production. These findings indicated that IS could induce MC proliferation via a COX-2-mediated mechanism, providing new insights into the understanding and therapies of progressive loss of RRF in ESRD.