Regulation and consequences of differential gene expression in diabetic kidney disease.
DN (diabetic nephropathy) is the leading cause of end-stage renal disease worldwide and develops in 25-40% of patients with Type 1 or Type 2 diabetes mellitus. Elevated blood glucose over long periods together with glomerular hypertension leads to progressive glomerulosclerosis and tubulointerstitial fibrosis in susceptible individuals. Central to the pathology of DN are cytokines and growth factors such as TGF-beta (transforming growth factor beta) superfamily members, including BMPs (bone morphogenetic protein) and TGF-beta1, which play key roles in fibrogenic responses of the kidney, including podocyte loss, mesangial cell hypertrophy, matrix accumulation and tubulointerstitial fibrosis. Many of these responses can be mimicked in in vitro models of cells cultured in high glucose. We have applied differential gene expression technologies to identify novel genes expressed in in vitro and in vivo models of DN and, importantly, in human renal tissue. By mining these datasets and probing the regulation of expression and actions of specific molecules, we have identified novel roles for molecules such as Gremlin, IHG-1 (induced in high glucose-1) and CTGF (connective tissue growth factor) in DN and potential regulators of their bioactions.
Murphy
Madeline
M
UCD Diabetes Research Centre, UCD Conway Institute, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
Crean
John
J
Brazil
Derek P
DP
Sadlier
Denise
D
Martin
Finian
F
Godson
Catherine
C
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D055513:Connective Tissue Growth Factor; D016208:Databases, Factual; D003928:Diabetic Nephropathies / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D044045:Lipoxins / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism
D001786:Blood Glucose; C526317:CCN2 protein, human; C486399:GREM1 protein, human; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D044045:Lipoxins; D011506:Proteins; C532028:THG1L protein, human; D055513:Connective Tissue Growth Factor