Disparate phospho-Smad2 levels in advanced type 2 diabetes patients with diabetic nephropathy and early experimental db/db mouse model.
Ren Fail
; 39(1): 629-642, 2017 Nov.
Article
en En
| MEDLINE
| ID: mdl-28805484
ABSTRACT
Uncontrolled activation of transforming growth factor beta (TGF-ß) family members is hypothesized to participate in type 2 diabetes (T2D) dependent diabetic nephropathy (DN). We evaluated and compared downstream activation of the Smad2-signaling pathway in kidney samples from T2D patients to kidneys from the T2D model of leptin receptor deficient db/db mouse. Furthermore, expression of TGF-ß family members was evaluated to elucidate molecular mechanisms in the mouse model. Kidney samples from patients with advanced stages of DN showed elevated pSmad2 staining whereas db/db mouse kidneys surprisingly showed a decrease in pSmad2 in the tubular compartment. Structurally, kidney tissue showed dilated tubules and expanded glomeruli, but no clear fibrotic pattern was found in the diabetic mice. Selective TGF-ß family members were up-regulated at the mRNA level. Antagonists of bone morphogenetic protein (BMP) ligands, such as Gremlin1, USAG1 and Sclerostin, were strongly up-regulated suggesting a dampening effect on BMP pathways. Together, these results indicate a lack of translation from T2D patient kidneys to the db/db model with regards to Smad signaling pathway. It is plausible that a strong up-regulation of BMP antagonizing factors account for the lack of Smad1/5/8 activation, in spite of increased expression of several BMP members.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Diabetes Mellitus Tipo 2
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Nefropatías Diabéticas
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Proteína Smad2
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Glomérulos Renales
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Túbulos Renales
Tipo de estudio:
Etiology_studies
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Prognostic_studies
Límite:
Adult
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Aged
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Aged80
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Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Ren Fail
Asunto de la revista:
NEFROLOGIA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Dinamarca