Connective tissue growth factor (CTGF) levels are up-regulated in patients with DN and in renal tubular epithelial cells (RTECs) exposed to high glucose (HG).
Our previous study demonstrated that fibroblast growth factor 21 (FGF21) prevented DN associated with the suppressing renal connective tissue growth factor expression, a key marker of renal fibrosis.
We have detected the expression of YAP, TEAD and CTGF in normal people (n=10) and patients with DN (n=51) by immunohistochemical and immunofluorescence staining and evaluated the relationship among clinical, pathologic data and YAP expression in type 2 diabetic nephropathy.
These above data suggested that overexpression of SHIP might be a potent method to lessen renal extracellular matrix accumulation via inactivation of PI3K/Akt pathway and suppression of CTGF expression in DKD.
Furthermore, blocking CTGF by specific antibody reduced albuminuria, prevented the overexpression of CTGF, as well as β-catenin, in glomeruli and subsequently ameliorated podocyte EMT in DN mice.
We found prominent lymphangiogenesis during tubulointerstitial fibrosis to be associated with increased expression of CTGF and VEGF-C in human obstructed nephropathy as well as in diabetic kidney disease.
By determining the expression of transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), collagen type IV (ColIV) and fibronectin (FN) levels in high glucose-cultured glomerular mesangial cells (MCs), the present study aimed to assess the anti-proliferative and anti-fibrotic effects of SIT on the therapeutic potential for the prevention of DN and its mechanism.
In this review, we only focus on the potential renoprotective therapeutic agents which can specifically abolish CCN2 expression or nonspecifically inhibit CCN2 expression for retarding the development and progression of DN.
TGFβ and CCN2 attenuate CREB and augment E2F1 transcriptional activation with the likely effect of altering actin cytoskeletal and cell growth/hypertrophic gene activity with implications for cell dysfunction in diabetic kidney disease.
Excessive growth of glomerular mesangial cells and overexpression of transforming growth factor-beta1 (TGF-beta1) and connective tissue growth factor (CTGF) are the pathological features of diabetic nephropathy.
Irbesartan ameliorates diabetic nephropathy by reducing the expression of connective tissue growth factor and alpha-smooth-muscle actin in the tubulointerstitium of diabetic rats.
Long-term inhibition and targeting TGFbeta(1) directly is problematic, therefore, a more fruitful direction targeting diabetic nephropathy may involve the development of therapeutic strategies specifically targeting CTGF.
Treatment with the CTGF ASO for 8 wk reduced serum creatinine and attenuated urinary albuminuria and proteinuria in diabetic db/db mice, a model of type 2 DN.
Connective tissue growth factor (CTGF/CCN2) is thought to play a role in normal wound repair and bone remodeling, but also promotes fibrosis in several disease processes including diabetic nephropathy, sclerodoma and pancreatitis.