Purchase this article with an account.
Louis Tong, Evelyn Png, Siew-Sian Yong; Transglutaminase-2 Is Critical For Wound Healing And Is Associated With Phosphorylation Of Key Proteins In Cell Matrix Adhesion. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4392.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Ocular surface diseases such as dry eye, persistent epithelial defects and pterygium involve aberrant wound healing. Transglutaminase (TGM)-2 is a ubiquitous protein that crosslinks substrates and also serves as a G protein, is also known to be involved in the cell signaling from adhesion complexes that influences cell migration. We aim to ascertain the role of TGM-2 in wound healing in an animal model, and whether it regulates the activation of cell adhesion proteins.
Homozygous TGM-2 deleted mice was used in the corneal wound healing model. In scratch assays, human corneal epithelial cells stably transfected with shRNA against TGM2 (shTG) were studied compared with cells transfected with scrambled shRNA (control). Western blots were performed against key phosphorylated cell adhesion proteins.
Closure of corneal wound was delayed in TGM-2 deleted mice compared to wildtype. Similarly shTG cells showed slower wound closure than control in scratch wound assays. Phosphorylation of β-1 integrin at Tyr785 was not affected by the TGM-2 status of the cells but phosphoryation of β-3 integrin at Tyr747, paxillin at Ser178 and vinculin at Tyr822 was reduced in shTG compared to control. Phosphorylation of focal adhesion kinase at Tyr 925 was reduced in shTG compared to control, but similar phosphorylation was present at Tyr 576. The total protein levels of these adhesion complex components were similar between shTG and control.
TGM-2 affects the phosphorylation of both early and late components of the cell-matrix adhesion complex. Through the activation of these components, TGM-2 regulates cell adhesion and migration and therefore corneal wound closure. These results suggest several targets for modulation of wound healing in the therapy of ocular surface diseases.
This PDF is available to Subscribers Only