Cell Injury, Repair, Aging and Apoptosis Tissue Transglutaminase Contributes to Interstitial Renal Fibrosis by Favoring Accumulation of Fibrillar Collagen through TGF- Activation

Renal fibrosis is defined by the exaggerated accumula-tion of extracellular matrix proteins. Tissue transglu-taminase (TG2) modifies the stability of extracellular matrix proteins and renders the extracellular matrix resistant to degradation. In addition, TG2 also activates transforming growth factor- (TGF-). We investigated the involvement of TG2 in the development of renal fibrosis using mice with a knockout of the TG2 gene (KO). These mice were studied at baseline and 12 days after unilateral ureteral obstruction, which induced a significant increase in interstitial TG2 expression in wild-type mice (P < 0.001). Interstitial fibrosis was evi-dent in both groups, but total and fibrillar collagen was considerably lower in KO mice as compared with wild-type (P < 0.001). Similarly, mRNA and protein expres