Connective tissue growth factor, matrix regulation, and diabetic kidney disease

Connective tissue growth factor, more recently officially known as CCN-2, is a member of the CCN family of secreted cysteine-rich modular matricellular proteins. Here, we review CCN-2 in diabetic nephropathy with focus on its regulation of extracellular matrix.

CCN-2 is upregulated in the clinical and preclinical models of diabetic nephropathy by multiple stimuli, including elevated glucose, advanced glycation, some types of lipid, various hemodynamic factors, as well as hypoxia and oxidative stress. CCN-2 has bioactivities that suggest it may mediate diabetic nephropathy pathogenesis, especially in extracellular matrix accumulation, through both induction of new matrix and inhibition of matrix degradation. CCN-2 also has proinflammatory functions. Moreover, recent studies using antibodies or antisense technologies in animal and early phase clinical trial settings have shown that inhibition of renal CCN-2 expression or action may prevent diabetic nephropathy. Additionally, determination of renal and blood levels of CCN-2 as a marker of diabetic renal disease and its progression appears to have value.

Recent publications implicate CCN-2 as both an evolving marker and mediator of diabetic nephropathy.