Identification of the role of TG2 on the expression of TGF-β, TIMP-1 and TIMP-2 in aged skin

Transglutaminase 2 (TG2) is a unique protein having enzymatic and nonenzymatic functions that have been implicated in various biological and pathological processes such as cell survival and apoptosis, cell signaling, differentiation, adhesion and migration, wound healing and inflammation. As reported in previous studies, TG2 expression and activity increase by age suggesting that TG2 possibly has roles in cellular aging process. In this study, we aimed to explore the role of TG2 in chronological skin aging through its impact on the expression of some important extracellular matrix (ECM) proteins including TGF-β, TIMP-1 and TIMP-2. We have compared TG2 expression and activity in young and in vitro chronologically aged human dermal fibroblasts via Western blot and in situ TG2 activity assays. Afterwards, we inhibited TG2 expression via siRNA transfection and activity via active site inhibitor of TG2 separately in aged dermal fibroblasts and monitored the expression levels of TGF-β, TIMP-1 and TIMP-2 in these cells by Western blot and compared to that of untreated control cells. We obtained evidence that both TG2 expression and activity increase in aged cells. However, protein levels of TGF-β, TIMP-1 and TIMP-2 do not exhibit any significant difference in TG2 downregulated or TG2 activity inhibited aged cells compared to control cells. Our results indicate that changes in the expression and activity of TG2 in (in vitro) chronologically aged human dermal fibroblasts do not impact the expression patterns of TGF-β, TIMP-1 and TIMP-2 proteins.