title: Impaired cornea wound healing in a tenascin C-deficient mouse model.
abstract: We investigated the effects of loss of tenascin C on the healing of the stroma using incision-injured mice corneas. Tenascin C was upregulated in the stroma following incision injury to the cornea. Wild-type (WT) and tenascin C-null (knockout (KO)) mice on a C57BL/6 background were used. Cell culture experiments were also conducted to determine the effects of the lack of tenascin C on fibrogenic gene expression in ocular fibroblasts. Histology, immunohistochemistry and real-time reverse transcription PCR were employed to evaluate the healing process in the stroma. The difference in the incidence of wound closure was statistically analyzed in hematoxylin and eosin-stained samples between WT and KO mice in addition to qualitative observation. Healing of incision injury in corneal stroma was delayed, with less appearance of myofibroblasts, less invasion of macrophages and reduction in expression of collagen Iα1, fibronectin and transforming growth factor β1 (TGFβ1) in KO mice compared with WT mice. In vitro experiments showed that the loss of tenascin C counteracted TGFβ1 acceleration of mRNA expression of TGFβ1, and of collagen Iα1 and of myofibroblast conversion in ocular fibroblasts. These results indicate that tenascin C modulates wound healing-related fibrogenic gene expression in ocular fibroblasts and is required for primary healing of the corneal stroma.
authors.affiliation: Department of Ophthalmology, Wakayama Medical University, Wakayama, Japan. sumioka@wakayama-med.ac.jp
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Sumioka
authors.forename: Ai
authors.initials: A
authors.lastname: Kitano
authors.forename: Kathleen C
authors.initials: KC
authors.lastname: Flanders
authors.forename: Yuka
authors.initials: Y
authors.lastname: Okada
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamanaka
authors.forename: Norihito
authors.initials: N
authors.lastname: Fujita
authors.forename: Hiroki
authors.initials: H
authors.lastname: Iwanishi
authors.forename: Winston W-Y
authors.initials: WW
authors.lastname: Kao
authors.forename: Shizuya
authors.initials: S
authors.lastname: Saika
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D024042:Collagen Type I / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D065306:Corneal Injuries; D003319:Corneal Stroma / Q000503:physiopathology*; D005353:Fibronectins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019063:Tenascin / Q000172:deficiency*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D005353:Fibronectins; D019063:Tenascin; D053773:Transforming Growth Factor beta1