alexa Expression of CD44s and CD44v3 by Proximal Tubules Influences the Renal Inflammatory Milieu-Induced by LPS Injection | OMICS International | Abstract
ISSN: 2161-0959

Journal of Nephrology & Therapeutics
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Research Article

Expression of CD44s and CD44v3 by Proximal Tubules Influences the Renal Inflammatory Milieu-Induced by LPS Injection

Elena Rampanelli1*, Nike Claessen1, Gwendoline JD Teske1, Jaklien C Leemans1 and Sandrine Florquin1,2

1Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands

2Department of Pathology, Radboud University Nijmegen Center, Nijmegen, Netherlands

*Corresponding Author:
Elena Rampanelli
Department of Pathology
Room L2-112, Academic Medical Center
P.O. Box 22660, 1100 AZ
Amsterdam, Netherland
Tel: +31-20-5665715
Fax: +31-20-6960389
E-mail: [email protected]

Received Date: November 16, 2014; Accepted Date: February 26, 2015; Published Date: March 03, 2015

Citation: Rampanelli E, Claessen N, Teske GJD, Leemans JC, Florquin S (2015) Expression of CD44s and CD44v3 by Proximal Tubules Influences the Renal Inflammatory Milieu-Induced by LPS Injection. J Nephrol Ther 5:196. doi:10.4172/2161-0959.1000196

Copyright: © 2015 Rampanelli E, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Systemic inflammatory response syndrome (SIRS) typically causes multiple-organ dysfunction/failure, including acute kidney injury (AKI). CD44 comprises a family of 85–200 kDa transmembrane glycoproteins that are widely expressed by multiple cell types and involved in a variety of inflammatory diseases. The multiple functions of CD44 have been attributed to the existence of numerous CD44 isoforms generated by alternative mRNA splicing as well as by extensive post-translational modifications. Renal CD44 expression is minimal in healthy adult kidneys, whereas in inflammatory renal disorders CD44 expression is markedly induced particularly in injured tubular epithelial cells (TEC) both in human diseases and in animal models. The function of CD44 on TEC remains unclear; previously we showed that the shortest isoform CD44 standard (CD44s) and the long CD44 variant 3-10 (CD44v3) exert opposite effects in fibrotic settings. To assess the contribution of tubular expression of CD44s and CD44v3 in SIRS-associated AKI, we used WT and unique transgenic mice expressing CD44s or CD44v3 specifically on proximal TEC. Mice were subjected to intraperitoneal injection of LPS and were sacrificed 4 and 24 hours later. The presence of CD44-isoforms in TEC did not alter the onset of kidney dysfunction or lymphocyte influx but affected the induction of KIM-1 and pro-/anti-inflammatory cytokines after LPS injection. Transgenic kidneys expressing CD44s/CD44v3 displayed more KIM-1 expression, less TNF-α and IL-1β at 4 hours compared to WT kidneys. At 24 hours, CD44v3-expressing kidneys showed elevated IL-10 and TLR4 negative regulator mRNA levels. Proximal TEC-CD44 influenced the renal inflammatory milieu and TEC-CD44v3 associated with expression of antiinflammatory molecules.

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