Comparative Analysis of KGF-2 and bFGF in Prevention of Excessive Wound Healing and Scar Formation in a Corneal Alkali Burn Model

PURPOSE: Basic fibroblast growth factor (bFGF) is an effective drug for corneal injury. However, the explicit role of bFGF in corneal scar formation still remains unclear. Keratinocyte growth factor-2 (KGF-2) is associated with the treatment of wound healing. We aimed to compare the efficacy of bFGF and KGF-2 in prevention of excessive wound healing and consequent scar formation in a rat alkali burn model, which provides important clues on the significance of KGF-2 to be developed as a new drug for such injuries. METHODS: The epithelial defect area was evaluated using fluorescein sodium at a concentration of 0.5%. The therapeutic effect of KGF-2 and bFGF on proliferation of rabbit corneal fibroblasts (RCFs) was evaluated by methylthiazoletetrazolium. RCF migration assays were performed with a modified scratch method. Activation of mitogen-activated protein kinase (MAPK) was evaluated by Western blot with specific antibodies. RESULTS: All corneal wounds treated with KGF-2 were found closed within 7 days; however, the wounds treated with bFGF or phosphate buffer saline (PBS) required 14 days to close. RCFs treated with KGF-2 or bFGF showed similar dose-dependent proliferation. The KGF-2 group significantly promoted cell migration compared with the bFGF group. The KGF-2 group showed less expression of α-smooth muscle actin (SMA) and numbers of myofibroblasts compared with the bFGF group. Our findings suggested identification of cascade reaction of extracellular regulated protein kinases (ERK)1/2 and p38 signals in KGF-2- and bFGF-induced proliferation and migration of RCFs. In addition, KGF-2 showed stronger effects during ERK1/2 and p38 phosphorylation in methylthiazoletetrazolium proliferation assay and scratch migration assay. CONCLUSIONS: KGF-2 exhibited better effects than bFGF in reepithelialization, acceleration of migration, and reduction of scar formation, which has potential to become a new drug to cure corneal injury.