Connective tissue growth factor (CTGF) expression modulates response to high
Authors James LR, Le C, Doherty H, Kim HS, Maeda N
Submitted By Nobuyo Maeda on 4/15/2014
Status Published
Journal PLoS ONE
Year 2013
Date Published
Volume : Pages 8 : e70441
PubMed Reference 23950936
Abstract Connective tissue growth factor (CTGF) is an important mediator of fibrosis;
emerging evidence link changes in plasma and urinary CTGF levels to diabetic
kidney disease. To further ascertain the role of CTGF in responses to high
glucose, we assessed the consequence of 4 months of streptozotocin-induced
diabetes in wild type (+/+) and CTGF heterozygous (+/-) mice. Subsequently, we
studied the influence of glucose on gene expression and protein in mice
embryonic fibroblasts (MEF) cells derived from wildtype and heterozygous mice.
At study initiation, plasma glucose, creatinine, triglyceride and cholesterol
levels were similar between non-diabetic CTGF+/+ and CTGF+/- mice. In the
diabetic state, plasma glucose levels were increased in CTGF+/+ and CTGF+/- mice
(28.2 3.3 mmol/L vs 27.0 3.1 mmol/L), plasma triglyceride levels were lower in
CTGF+/- mice than in CTGF+/+ (0.7 0.2 mmol/L vs 0.5 0.1 mmol/L, p<0.05), but
cholesterol was essentially unchanged in both groups. Plasma creatinine was
higher in diabetic CTGF+/+ group (11.7±1.2 vs 7.9±0.6 µmol/L p<0.01), while
urinary albumin excretion and mesangial expansion were reduced in diabetic
CTGF+/- animals. Cortices from diabetic mice (both CTGF +/+ and CTGF +/-)
manifested higher expression of CTGF and thrombospondin 1 (TSP1). Expression of
nephrin was reduced in CTGF +/+ animals; this reduction was attenuated in
CTGF+/- group. In cultured MEF from CTGF+/+ mice, glucose (25 mM) increased
expression of pro-collagens 1, IV and XVIII as well as fibronectin and
thrombospondin 1 (TSP1). In contrast, activation of these genes by high glucose
was attenuated in CTGF+/- MEF. We conclude that induction of Ctgf mediates
expression of extracellular matrix proteins in diabetic kidney. Thus, genetic
variability in CTGF expression directly modulates the severity of diabetic

Investigators with authorship
Nobuyo MaedaUniversity of North Carolina