Do changes in transglutaminase activity alter latent transforming growth factor beta activation in experimental diabetic nephropathy?

Diabetic nephropathy is the leading cause of end-stage kidney failure worldwide. It is characterized by excessive extracellular matrix accumulation. Transforming growth factor beta 1 (TGF-β1) is a fibrogenic cytokine playing a major role in the healing process and scarring by regulating extracellular matrix turnover, cell proliferation and epithelial mesanchymal transdifferentiation. Newly synthesized TGF-β is released as a latent, biologically inactive complex. The cross-linking of the large latent TGF-β to the extracellular matrix by transglutaminase 2 (TG2) is one of the key mechanisms of recruitment and activation of this cytokine. TG2 is an enzyme catalyzing an acyl transfer reaction leading to the formation of a stable ε(γ-glutamyl)-lysine cross-link between peptides.