CCN2 and Hyperglycemia: Insulin like growth factor-1 (IGF-1) and dedifferentiation of vascular smooth muscle cells can induce connected tissue growth factor (CTGF), thus promoting renal tubular fibrosis Hyperglycemia in rat mesangial cells inhibits the degradation of the extracellular matrix by metalloproteinase 9, resulting in mesangial extracellular matrix proliferation and fibrosis (47–50).