Allelic depletion of grem1 attenuates diabetic kidney disease.


Autoria(s): Roxburgh, Sarah A.; Kattla, J.J.; Curran, S.P.; O'Meara, Yvonne M.; Pollock, Carol A.; Goldschemding, Roel; Godson, Catherine; Martin, Finian; Brazil, Derek P.
Data(s)

01/07/2009

Resumo

OBJECTIVE: Gremlin (grem1) is an antagonist of the bone morphogenetic protein family that plays a key role in limb bud development and kidney formation. There is a growing appreciation that altered grem1 expression may regulate the homeostatic constraints on damage responses in diseases such as diabetic nephropathy. RESEARCH DESIGN AND METHODS: Here we explored whether knockout mice heterozygous for grem1 gene deletion (grem1(+/-)) exhibit protection from the progression of diabetic kidney disease in a streptozotocin-induced model of type 1 diabetes. RESULTS: A marked elevation in grem1 expression was detected in the kidneys and particularly in kidney tubules of diabetic wild-type mice compared with those of littermate controls. In contrast, diabetic grem1(+/-) mice displayed a significant attenuation in grem1 expression at 6 months of diabetes compared with that in age- and sex-matched wild-type controls. Whereas the onset and induction of diabetes were similar between grem1(+/-) and wild-type mice, several indicators of diabetes-associated kidney damage such as increased glomerular basement membrane thickening and microalbuminuria were attenuated in grem1(+/-) mice compared with those in wild-type controls. Markers of renal damage such as fibronectin and connective tissue growth factor were elevated in diabetic wild-type but not in grem1(+/-) kidneys. Levels of pSmad1/5/8 decreased in wild-type but not in grem1(+/-) diabetic kidneys, suggesting that bone morphogenetic protein signaling may be maintained in the absence of grem1. CONCLUSIONS: These data identify grem1 as a potential modifier of renal injury in the context of diabetic kidney disease.

Identificador

http://pure.qub.ac.uk/portal/en/publications/allelic-depletion-of-grem1-attenuates-diabetic-kidney-disease(8a687f4f-80aa-4813-a176-2ae4871cf1f9).html

http://dx.doi.org/10.2337/db08-1365

Idioma(s)

eng

Direitos

info:eu-repo/semantics/restrictedAccess

Fonte

Roxburgh , S A , Kattla , J J , Curran , S P , O'Meara , Y M , Pollock , C A , Goldschemding , R , Godson , C , Martin , F & Brazil , D P 2009 , ' Allelic depletion of grem1 attenuates diabetic kidney disease. ' Diabetes , vol 58 , no. 7 , pp. 1641-1650 . DOI: 10.2337/db08-1365

Palavras-Chave #/dk/atira/pure/subjectarea/asjc/2700/2712 #Endocrinology, Diabetes and Metabolism #/dk/atira/pure/subjectarea/asjc/2700/2724 #Internal Medicine
Tipo

article