| First Author | Okada Y | Year | 2014 |
| Journal | Lab Invest | Volume | 94 |
| Issue | 9 | Pages | 1030-41 |
| PubMed ID | 25068659 | Mgi Jnum | J:214841 |
| Mgi Id | MGI:5604067 | Doi | 10.1038/labinvest.2014.85 |
| Citation | Okada Y, et al. (2014) TRPA1 is required for TGF-beta signaling and its loss blocks inflammatory fibrosis in mouse corneal stroma. Lab Invest 94(9):1030-41 |
| abstractText | We examined whether the loss of transient receptor potential ankyrin 1 (TRPA1), an irritant-sensing ion channel, or TRPA1 antagonist treatment affects the severity inflammation and scarring during tissue wound healing in a mouse cornea injury model. In addition, the effects of the absence of TRPA1 on transforming growth factor beta1 (TGF-beta1)-signaling activation were studied in cell culture. The lack of TRPA1 in cultured ocular fibroblasts attenuated expression of TGF-beta1, interleukin-6, and alpha-smooth muscle actin, a myofibroblast the marker, but suppressed the activation of Smad3, p38 MAPK, ERK, and JNK. Stroma of the healing corneas of TRPA1(-/-) knockout (KO) mice appeared more transparent compared with those of wild-type mice post-alkali burn. Eye globe diameters were measured from photographs. An examination of the corneal surface and eye globes suggested the loss of TRPA1 suppressed post-alkali burn inflammation and fibrosis/scarring, which was confirmed by histology, immunohistochemistry, and gene expression analysis. Reciprocal bone marrow transplantation between mice showed that KO corneal tissue resident cells, but not KO bone marrow-derived cells, are responsible for KO mouse wound healing with reduced inflammation and fibrosis. Systemic TRPA1 antagonists reproduced the KO phenotype of healing. In conclusion, a loss or blocking of TRPA1 in mice reduces inflammation and fibrosis/scarring in the corneal stroma during wound healing following an alkali burn. The responsible mechanism may include the inhibition of TGF-beta1-signaling cascades in fibroblasts by attenuated TRPA1 signaling. Inflammatory cells are considered to have a minimum involvement in the exhibition of the KO phenotype after injury. |
