Neuroblastoma suppressor of tumorigenicity 1 is a circulating protein associated with progression to end-stage kidney disease in diabetes.
Journal
Science translational medicine
ISSN: 1946-6242
Titre abrégé: Sci Transl Med
Pays: United States
ID NLM: 101505086
Informations de publication
Date de publication:
10 08 2022
10 08 2022
Historique:
entrez:
10
8
2022
pubmed:
11
8
2022
medline:
13
8
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35947673
doi: 10.1126/scitranslmed.abj2109
pmc: PMC9531292
mid: NIHMS1837259
doi:
Substances chimiques
Cell Cycle Proteins
0
NBL1 protein, human
0
Transforming Growth Factor beta
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Intramural
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
eabj2109Subventions
Organisme : NIDDK NIH HHS
ID : K08 DK126847
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG024824
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK126799
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK036836
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK110350
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK041526
Pays : United States
Commentaires et corrections
Type : CommentIn
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