Senescence marker activin A is increased in human diabetic kidney disease: association with kidney function and potential implications for therapy.
Activins
/ blood
Adult
Aged
Biomarkers
/ blood
Case-Control Studies
Cells, Cultured
Cellular Senescence
Cohort Studies
Diabetes Mellitus, Type 2
/ blood
Diabetic Nephropathies
/ blood
Female
Glomerular Filtration Rate
Humans
Ireland
/ epidemiology
Kidney
/ physiopathology
Male
Middle Aged
Minnesota
/ epidemiology
adipocytokine
clinical aspects of diabetes
clinical nephrology
renal fibrosis
Journal
BMJ open diabetes research & care
ISSN: 2052-4897
Titre abrégé: BMJ Open Diabetes Res Care
Pays: England
ID NLM: 101641391
Informations de publication
Date de publication:
2019
2019
Historique:
received:
27
06
2019
revised:
28
09
2019
accepted:
23
10
2019
entrez:
8
1
2020
pubmed:
8
1
2020
medline:
1
9
2020
Statut:
epublish
Résumé
Activin A, an inflammatory mediator implicated in cellular senescence-induced adipose tissue dysfunction and profibrotic kidney injury, may become a new target for the treatment of diabetic kidney disease (DKD) and chronic kidney diseases. We tested the hypothesis that human DKD-related injury leads to upregulation of activin A in blood and urine and in a human kidney cell model. We further hypothesized that circulating activin A parallels kidney injury markers in DKD. In two adult diabetes cohorts and controls (Minnesota, USA; Galway, Ireland), the relationships between plasma (or urine) activin A, estimated glomerular filtration rate (eGFR) and DKD injury biomarkers were tested with logistic regression and correlation coefficients. Activin A, inflammatory, epithelial-mesenchymal-transition (EMT) and senescence markers were assayed in human kidney (HK-2) cells incubated in high glucose plus transforming growth factor-β1 or albumin. Plasma activin A levels were elevated in diabetes (n=206) compared with controls (n=76; 418.1 vs 259.3 pg/mL; p<0.001) and correlated inversely with eGFR (r Circulating activin A is increased in human DKD and correlates with reduced kidney function and kidney injury markers. DKD-injured human renal tubule cells develop a profibrotic and inflammatory phenotype with activin A upregulation. These findings underscore the role of inflammation and provide a basis for further exploration of activin A as a diagnostic marker and therapeutic target in DKD.
Identifiants
pubmed: 31908790
doi: 10.1136/bmjdrc-2019-000720
pii: bmjdrc-2019-000720
pmc: PMC6936543
doi:
Substances chimiques
Biomarkers
0
activin A
0
Activins
104625-48-1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e000720Subventions
Organisme : NIDDK NIH HHS
ID : K23 DK114497
Pays : United States
Organisme : NIDDK NIH HHS
ID : K23 DK109134
Pays : United States
Organisme : NIDDK NIH HHS
ID : K08 DK118120
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000135
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM065841
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK100081
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK102325
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002377
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK120292
Pays : United States
Informations de copyright
© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.
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