Type

Journal Article

Authors

Derek P. Brazil
Finian Martin
Catherine Godson
Roel Goldschmeding
Carol A Pollock
Yvonne M O'Meara
Simon P Curran
Jayesh J Kattla
Sarah A Roxburgh

Subjects

Biochemistry

Topics
grem1 protein mouse mice knockout blood male deficiency urine pathology albuminuria lipids gene deletion animals physiopathology creatinine prevention control genetics mice homeostasis complications metabolism hemoglobin a glycosylated diabetic nephropathies intercellular signaling peptides and proteins diabetes mellitus experimental

Allelic depletion of grem1 attenuates diabetic kidney disease. (2009)

Abstract 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. 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. 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. These data identify grem1 as a potential modifier of renal injury in the context of diabetic kidney disease.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Derek P. Brazil, Finian Martin, Catherine Godson, Roel Goldschmeding, Carol A Pollock, Yvonne M O'Meara, Simon P Curran, Jayesh J Kattla, Sarah A Roxburgh

Experts in our system

1
Derek P. Brazil
University College Dublin
Total Publications: 28
 
2
Finian Martin
University College Dublin
Total Publications: 81
 
3
Catherine Godson
University College Dublin
Total Publications: 93
 
4
Roel Goldschmeding
University College Dublin
Total Publications: 4