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Neuroblastoma suppressor of tumorigenicity 1 is a circulating protein associated with progression to end-stage kidney disease in diabetes.
Kobayashi, Hiroki; Looker, Helen C; Satake, Eiichiro; D'Addio, Francesca; Wilson, Jonathan M; Saulnier, Pierre Jean; Md Dom, Zaipul I; O'Neil, Kristina; Ihara, Katsuhito; Krolewski, Bozena; Badger, Hannah S; Petrazzuolo, Adriana; Corradi, Domenico; Galecki, Andrzej; Wilson, Parker C; Najafian, Behzad; Mauer, Michael; Niewczas, Monika A; Doria, Alessandro; Humphreys, Benjamin D; Duffin, Kevin L; Fiorina, Paolo; Nelson, Robert G; Krolewski, Andrzej S.
Afiliación
  • Kobayashi H; Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center, Boston, MA 02215, USA.
  • Looker HC; Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
  • Satake E; Division of Nephrology, Hypertension, and Endocrinology, Nihon University School of Medicine, Tokyo 173-8610, Japan.
  • D'Addio F; Chronic Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ 85014, USA.
  • Wilson JM; Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center, Boston, MA 02215, USA.
  • Saulnier PJ; Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
  • Md Dom ZI; Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, DIBIC L. Sacco, Università di Milano and Endocrinology Division ASST Sacco-FBF, Milan 20121, Italy.
  • O'Neil K; Diabetes and Complications Department, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46225, USA.
  • Ihara K; Chronic Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ 85014, USA.
  • Krolewski B; CHU Poitiers, University of Poitiers, Inserm, Clinical Investigation Center CIC1402, Poitiers 86000, France.
  • Badger HS; Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center, Boston, MA 02215, USA.
  • Petrazzuolo A; Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
  • Corradi D; Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center, Boston, MA 02215, USA.
  • Galecki A; Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center, Boston, MA 02215, USA.
  • Wilson PC; Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
  • Najafian B; Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center, Boston, MA 02215, USA.
  • Mauer M; Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
  • Niewczas MA; Diabetes and Complications Department, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46225, USA.
  • Doria A; Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, DIBIC L. Sacco, Università di Milano and Endocrinology Division ASST Sacco-FBF, Milan 20121, Italy.
  • Humphreys BD; Department of Medicine and Surgery, Unit of Pathology, University of Parma, Parma 43126, Italy.
  • Duffin KL; Department of Internal Medicine, Medical School, University of Michigan, Ann Arbor, MI 48109, USA.
  • Fiorina P; Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI 48109-2029, USA.
  • Nelson RG; Division of Anatomic and Molecular Pathology, Department of Pathology and Immunology, Washington University in Saint Louis School of Medicine, St. Louis 63110, USA.
  • Krolewski AS; Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA 98109, USA.
Sci Transl Med ; 14(657): eabj2109, 2022 08 10.
Article en En | MEDLINE | ID: mdl-35947673
Circulating proteins associated with transforming growth factor-ß (TGF-ß) 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-ß 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Ciclo Celular / Diabetes Mellitus Tipo 2 / Fallo Renal Crónico / Neuroblastoma Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Sci Transl Med Asunto de la revista: CIENCIA / MEDICINA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Ciclo Celular / Diabetes Mellitus Tipo 2 / Fallo Renal Crónico / Neuroblastoma Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Sci Transl Med Asunto de la revista: CIENCIA / MEDICINA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos