Abstract
Purpose: :
To evaluate anti–fibrogenic effects of suppression of p38 mitogen–activated kinase (MAPK) by adenoviral gene transfer of dominant–negative (DN) p38MAPK in a mouse model of post–injury conjuctival scarring. We reported the role of p38MAPK signal on fibrogenic reaction of cultured subconjunctival fibroblasts in vitro by using a specific inhibitor (2003, ARVO).
Methods: :
A circumferential incision was made in conjunctiva in the equator by using scissors in the right eye of generally anesthized adult C57BL/6 mice (n = 75). DN–p38MAPK adenoviruses were topically applied. Efficacy of adenoviral gene transfer by this system was previously established by us. On day 2, 5, and 7, the eyes were processed for immunohistochemical examination, RNA extraction and real time RT–PCR for cytokine expression.
Results: :
DN–p38MAPK treatment reduced protein expression of phospho–p38MAPK as compared with control eyes with non–functioning vector. Expression of type I collagen, connective tissue growth factor (CTGF), generation of smooth muscle actin–positive myofibroblasts and invasion of F4/80–labeled macrophages were all less in the DN–p38MAPK–adenoivirus groups as compared with control. Expression of collagen Ia2 and CTGF mRNA were both reduced by DN–p38MAPK gene introduction.
Conclusions: :
Suppression of p38MAPK attenuated the post–injury conjunctival fibrogenic reaction in vivo in mice, supporting its effectiveness in preventing/treating conjunctival scarring.
Keywords: gene transfer/gene therapy • wound healing • signal transduction