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Abstract #19780 Published in IGR 9-4
Inhibition of p38MAP kinase suppresses fibrogenic reaction in conjunctiva in mice
Yamanaka O; Saika S; Ohnishi Y; Kim-Mitsuyama S; Kamaraju AK; Ikeda KMolecular Vision 2007; 13: 1730-1739
PURPOSE: To examine the effects of blocking p38 mitogen-activated protein kinase (MAPK) on post-injury conjunctival scarring in mices. Its effect on the behaviors of cultured subconjunctival fibroblasts were also investigated. METHODS: An in-vivo study was conducted using an adenoviral vector carrying a dominant-negative (DN)-p38MAPK gene. A circumferential incision was made in the equatorial conjunctiva by scissors in the right eye of generally anesthetized adult C57BL/6 mice. DN-p38MAPK-expressing adenoviral vector was topically applied. The left control eye received non-functioning adenoviral vector. At two, five, and seven days (each, n = 22) the eyes were processed for histological or immunohistochemical examination to evaluate the tissue scarring. The expressions of type-I collagen and growth factors were evaluated by real time-reverse transcriptase-polymerase chain reaction. The effects of p38MAPK inhibitor on the proliferation, migration, and fibrogenic gene/protein expression of cultured human fibroblasts were also studied. RESULTS: The in-vivo DN-p38MAPK gene introduction blocked the phospho-p38 expression with reduction of myofibroblast generation and suppression of mRNA expression of connective tissue growth factor (CTGF) and monocyte/macrophage chemoattractant protein-1 (MCP-1) in the mouse-injured conjunctiva. Blocking p38MAPK signal in the fibroblasts by a chemical inhibitor counteracted TGFβ1's enhancement of expressions of type-I collagen, fibronectin, and CTGR. It also retarded cell migration, but cell proliferation was unchanged. CONCLUSIONS: Inhibiting p38MAPK signal impairs the fibrogenic reaction induced by the subconjunctival fibroblasts in vivo and in vitro, suggesting its potential effectiveness in preventing excessive scarring following glaucoma filtering surgery.
Dr. O. Yamanaka, Department of Ophthalmology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-0012, Japan. yamanaka@wakayama-med.ac.jp
Classification:
12.8.10 Woundhealing antifibrosis (Part of: 12 Surgical treatment > 12.8 Filtering surgery)
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)