Neuroblastoma suppressor of tumorigenicity 1 is a circulating protein associated with progression to end-stage kidney disease in diabetes-Reference-Cited by-同舟云学术

Neuroblastoma suppressor of tumorigenicity 1 is a circulating protein associated with progression to end-stage kidney disease in diabetes

Published:2022-08-10 Issue:657 Volume:14 Page:
ISSN:1946-6234
Container-title:Science Translational Medicine
language:en
Short-container-title:Sci. Transl. Med.

Author:

Kobayashi Hiroki¹²³^ORCID,Looker Helen C.⁴,Satake Eiichiro¹²^ORCID,D’Addio Francesca⁵^ORCID,Wilson Jonathan M.⁶^ORCID,Saulnier Pierre Jean⁴⁷^ORCID,Md Dom Zaipul I.¹²^ORCID,O’Neil Kristina¹^ORCID,Ihara Katsuhito¹²^ORCID,Krolewski Bozena¹²,Badger Hannah S.⁶^ORCID,Petrazzuolo Adriana⁵^ORCID,Corradi Domenico⁸^ORCID,Galecki Andrzej⁹¹⁰,Wilson Parker C.¹¹^ORCID,Najafian Behzad¹²^ORCID,Mauer Michael¹³^ORCID,Niewczas Monika A.¹²^ORCID,Doria Alessandro¹²^ORCID,Humphreys Benjamin D.¹⁴^ORCID,Duffin Kevin L.⁶^ORCID,Fiorina Paolo⁵¹⁵^ORCID,Nelson Robert G.⁴^ORCID,Krolewski Andrzej S.¹²^ORCID

Affiliation:

1. Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center, Boston, MA 02215, USA.

2. Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.

3. Division of Nephrology, Hypertension, and Endocrinology, Nihon University School of Medicine, Tokyo 173-8610, Japan.

4. Chronic Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ 85014, USA.

5. Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, DIBIC L. Sacco, Università di Milano and Endocrinology Division ASST Sacco-FBF, Milan 20121, Italy.

6. Diabetes and Complications Department, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46225, USA.

7. CHU Poitiers, University of Poitiers, Inserm, Clinical Investigation Center CIC1402, Poitiers 86000, France.

8. Department of Medicine and Surgery, Unit of Pathology, University of Parma, Parma 43126, Italy.

9. Department of Internal Medicine, Medical School, University of Michigan, Ann Arbor, MI 48109, USA.

10. Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI 48109-2029, USA.

11. Division of Anatomic and Molecular Pathology, Department of Pathology and Immunology, Washington University in Saint Louis School of Medicine, St. Louis 63110, USA.

12. Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA 98109, USA.

13. Department of Pediatrics and Medicine, University of Minnesota, Minneapolis, MN 55455, USA.

14. Division of Nephrology, Department of Medicine, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA.

15. Nephrology Division, Boston Children’s Hospital, Boston, MA 02115, USA.

Abstract

Circulating proteins associated with transforming growth factor–β (TGF-β) signaling are implicated in the development of diabetic kidney disease (DKD). It remains to be comprehensively examined which of these proteins are involved in the pathogenesis of DKD and its progression to end-stage kidney disease (ESKD) in humans. Using the SOMAscan proteomic platform, we measured concentrations of 25 TGF-β signaling family proteins in four different cohorts composed in total of 754 Caucasian or Pima Indian individuals with type 1 or type 2 diabetes. Of these 25 circulating proteins, we identified neuroblastoma suppressor of tumorigenicity 1 (NBL1, aliases DAN and DAND1), a small secreted protein known to inhibit members of the bone morphogenic protein family, to be most strongly and independently associated with progression to ESKD during 10-year follow-up in all cohorts. The extent of damage to podocytes and other glomerular structures measured morphometrically in 105 research kidney biopsies correlated strongly with circulating NBL1 concentrations. Also, in vitro exposure to NBL1 induced apoptosis in podocytes. In conclusion, circulating NBL1 may be involved in the disease process underlying progression to ESKD, and its concentration in circulation may identify subjects with diabetes at increased risk of progression to ESKD.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine

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