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Intercellular adhesion molecule-1 plays a critical role in glomerulosclerosis after subtotal nephrectomy

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Abstract

Background

Hyperfiltration in the glomeruli have been considered to be an important cause of glomerular injury; however, the role of intercellular adhesion molecule (ICAM)-1 in the pathogenesis of glomerulosclerosis is not known.

Methods

To elucidate the effects of ICAM-1 depletion on hyperfiltration-induced glomerular disorder, we used subtotally nephrectomized ICAM-1+/+ and ICAM-1−/− mice. We evaluated macrophage infiltration, mesangial matrix expansion, transforming growth factor (TGF)-β and type IV collagen accumulation in glomeruli.

Results

Macrophage infiltration into the glomeruli and mesangial matrix expansion coincident with increased expression of both ICAM-1 and TGF-β, and accumulation of type IV collagen were ameliorated in subtotally nephrectomized ICAM-1−/− mice compared to ICAM-1+/+ mice. ICAM-1 depletion significantly reduced hyperfiltration-induced glomerular injury after renal ablation.

Conclusions

Our present findings suggest that glomerular hyperfiltration is the leading cause of glomerulosclerosis, and it is mediated, at least in part, by ICAM-1 expression and macrophage infiltration.

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Acknowledgments

This study was supported in part by Grant-in-Aid for Scientific Research (C) to K. Shikata (21591031) and Grant-in-Aid for Young Scientists (B) to D. Ogawa (21790813) from the Ministry of Education, Culture, Sports, Science and Technology, Japan. This work has received support from the Takeda Science Foundation and the Naito Foundation.

Conflict of interest

The authors have declared that no Conflict of interest exists.

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Authors and Affiliations

  1. Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan

    Yuichi Kido, Daisuke Ogawa, Kenichi Shikata, Motofumi Sasaki, Ryo Nagase, Shinichi Okada, Hitomi Usui Kataoka, Jun Wada & Hirofumi Makino

  2. Department of Diabetic Nephropathy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    Daisuke Ogawa

  3. Department of Primary Care and Medical Education, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    Hitomi Usui Kataoka

  4. Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan

    Kenichi Shikata

Authors
  1. Yuichi Kido
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  2. Daisuke Ogawa
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  3. Kenichi Shikata
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  4. Motofumi Sasaki
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  5. Ryo Nagase
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  6. Shinichi Okada
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  7. Hitomi Usui Kataoka
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  8. Jun Wada
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  9. Hirofumi Makino
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Corresponding author

Correspondence to Kenichi Shikata.

Additional information

Y. Kido and D. Ogawa equally contributed to this work.

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Kido, Y., Ogawa, D., Shikata, K. et al. Intercellular adhesion molecule-1 plays a critical role in glomerulosclerosis after subtotal nephrectomy. Clin Exp Nephrol 15, 212–219 (2011). https://doi.org/10.1007/s10157-010-0388-7

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  • DOI: https://doi.org/10.1007/s10157-010-0388-7

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