title: Wakayama symposium: modulation of wound healing response in the corneal stroma by osteopontin and tenascin-C.
abstract: The extracellular matrix components osteopontin and tenascin-C are ligands of α9 integrin, and both play roles in corneal wound fibrosis and neovascularization. It has been shown that loss of osteopontin impairs closure of incisional wounds in the mouse cornea. Detailed analyses suggest that the loss of osteopontin reduces macrophage invasion and myofibroblast differentiation in the healing stroma in association with suppression of fibrogenic gene expression in response to injury. Cultured ocular fibroblasts derived from knockout mice showed an impairment of activation of p38 MAPK and Smad3 upon exposure to transforming growth factor β1. The loss of tenascin-C delays stromal healing in association with suppression of fibrogenic gene expression and macrophage invasion. With regard to neovascularization, the loss of either osteopontin or tenascin-C suppressed the growth of new blood vessels from the limbal region toward the central cornea in response to corneal cauterization in mice. Gene expression analysis further showed that lack of osteopontin or tenascin-C resulted in inhibition of angiogenic and proinflammatory gene expression. In conclusion, osteopontin or tenascin-C, α9 integrin ligands, play an important role in stromal healing (or fibrosis) and neovascularization in mouse cornea.
authors: Department of Ophthalmology, Wakayama Medical University, Wakayama, Japan. shizuya@wakayama-med.ac.jp
authors: Shizuya
authors: S
authors: Saika
authors: Takayoshi
authors: T
authors: Sumioka
authors: Yuka
authors: Y
authors: Okada
authors: Osamu
authors: O
authors: Yamanaka
authors: Ai
authors: A
authors: Kitano
authors: Takeshi
authors: T
authors: Miyamoto
authors: Kumi
authors: K
authors: Shirai
authors: Hideaki
authors: H
authors: Kokado
mesh_terms: D000818:Animals; D003319:Corneal Stroma / Q000378:metabolism*; D005136:Eye Proteins / Q000502:physiology*; D006801:Humans; D039001:Integrin alpha Chains / Q000502:physiology; D053495:Osteopontin / Q000502:physiology*; D019063:Tenascin / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology*
chemical_list: D005136:Eye Proteins; D039001:Integrin alpha Chains; D019063:Tenascin; C084613:integrin alpha9; D053495:Osteopontin