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Glomerular expression of transforming growth factor–β (TGF-β) isoforms in mice lacking CD2-associated protein

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Abstract

Mice lacking CD2-associated protein (CD2AP−/−) develop glomerular lesions resembling human focal segmental glomerulosclerosis (FSGS) between 3–4 weeks of age and die approximately 2 weeks later from massive proteinuria and renal failure. The mechanisms involved in the glomerular injury in this model are unclear. In this study, we used laser capture microdissection (LCM) and real-time PCR, and examined expression of TGF-ß isoforms in CD2AP−/− mice at the level of isolated glomeruli. Total RNA yield from cryosections of 30 glomeruli was 10.71 ng (SD, 5.45) in CD2AP+/+ group (n =7), and 4.20 ng (SD, 2.04) in CD2AP−/− group (n =8), p =0.008. Expression of TGF-ß1 mRNA was increased 1.5-fold in the whole kidney (p =0.030), and twofold in isolated CD2AP−/− glomeruli (p =0.026). Whole kidney mRNA of TGF-ß receptor I (RI) and II (RII) was not different in CD2AP−/− and CD2AP+/+ animals, but it was increased in CD2AP−/− glomerular samples by 4.38-fold (p =0.001) and 11.37-fold (p =0.0163), respectively. By using LCM we confirmed increased glomerular expression levels of TGF-ß isoforms previously described by our group in glomeruli isolated by sieving in CD2AP KO mice and underscored the importance of local factors in the development of glomerulosclerosis.

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Acknowledgements

This work was supported in part by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (5U24DK058768–03), National Institute of Health Training grant (DK07110–27), and the Emerald Foundation, Inc.

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  1. Mario Schiffer

    Present address: Hannover Medical School, Division of Nephrology, 30625, Hannover, Germany

Authors and Affiliations

  1. Section of Pediatric Nephrology, Children’s Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, 10467, USA

    Robert P. Woroniecki & Frederick J. Kaskel

  2. Department of Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY, 10029, USA

    Mario Schiffer & Erwin P. Bottinger

  3. Department of Pathology and Immunology, Washington University, 660 South Euclid, Box 8118, St. Louis, MO, 63110, USA

    Andrey S. Shaw

Authors
  1. Robert P. Woroniecki
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  2. Mario Schiffer
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  3. Andrey S. Shaw
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  4. Frederick J. Kaskel
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  5. Erwin P. Bottinger
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Corresponding authors

Correspondence to Frederick J. Kaskel or Erwin P. Bottinger.

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Woroniecki, R.P., Schiffer, M., Shaw, A.S. et al. Glomerular expression of transforming growth factor–β (TGF-β) isoforms in mice lacking CD2-associated protein. Pediatr Nephrol 21, 333–338 (2006). https://doi.org/10.1007/s00467-005-2102-7

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  • DOI: https://doi.org/10.1007/s00467-005-2102-7

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