[Frontiers in Bioscience 14, 3814-3824, January 1, 2009]

[Frontiers in Bioscience 14, 3814-3824, January 1, 2009]

Effects of DC-SIGN expression on renal tubulointerstitial fibrosis in nephritis

Tong Zhou¹, Xiao Li¹, Jie Zou¹, Minchao Cai¹, Guizhi Sun¹, Yumei Zhang¹, Yapeng Zhao¹, Mingjun Zhang², Yanyun Zhang³, Nan Chen¹

1Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui jin Er road, Shanghai 200025, China,²Laboratory of Animal, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui jin Er road, Shanghai 200025, China, ³Shanghai Institute of Immunology and Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 227 South Chongqing Road, Shanghai 200025, China

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Materials and methods: 3.1. Animals and reagents; 3.2. Patients; 3.3. Animal models; 3.4. Biochemical analysis and histopathologic measurement in rats; 3.5. Detection of DC-SIGN expression in renal tissues; 3.6. Immunofluorescent staining for DC-SIGN+ DC distribution in renal tissues; 3.7. Analysis of DC-SIGN on HK-2 cells; 3.8. Analysis of DC-SIGN mRNA and CD80 mRNA on HK-2 cells; 3.9. Statistical analysis
4. Results: 4.1. DC-SIGN expression in renal tissues; 4.2. DC-SIGN+ DC distribution in renal tissues; 4.3. Expression of DC-SIGN, DC-SIGN mRNA, and CD80 mRNA on HK-2 cells; 4.4. Renal histopathology and renal function changes in rats with chronic renal interstitial fibrosis; 4.5. Fibrogenic factors and extracellular matrix (ECM) changes in renal tissues of rats with chronic renal interstitial fibrosis; 4.6. DC-SIGN expression and DC-SIGN+ DC distribution in renal tissues of rats with chronic renal interstitial fibrosis
5. Discussion
6. Acknowledgements
7. References

1. ABSTRACT

Dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) is important for dendritic cell (DC) in migrating, recognizing, capturing, presenting antigens and in initiating T cell responses. In the present study, we investigated the role of DC-SIGN in renal tubulointerstitial inflammation and fibrosis. DC-SIGN was mainly expressed in tubular epithelial cells and DC-SIGN⁺DCs were primarily distributed in renal tubulointerstitial areas during the early stage of nephritis, which was correlated with the degree of renal tubular interstitial lesions and fibrosis. In vitro, DC-SIGN expression in cultured human renal tubular epithelial cells was elevated when treated by tumor necrosis factor-alpha, and was inhibited by anti-P-selectin lectin-EGF domain monoclonal antibody (PsL-EGFmAb). In a rat model of chronic renal interstitial fibrosis, there was a significant correlation of DC-SIGN expression with DC-SIGN⁺DC distribution and the degree of tubulointerstitial lesion. PsL-EGFmAb reduced DC-SIGN expression and DC-SIGN⁺ DC accumulation in renal tissues in this rat model. These results suggest that DC-SIGN plays an important role in DC-mediated renal tubular interstitial lesions induced by immuno-inflammatory responses.