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

Cai, JianQiu MBBS*,†; Zhou, Qingde MSc; Wang, Zhitao MSc; Guo, Ruide MBBS; Yang, Rongshuai MSc; Yang, Xuanxin MSC; Li, Wenqing MSc; Ahmad, Naveed PhD§; Chen, Qi MBBS†,¶; Hui, Qi PhD*,†; Wang, Xiaojie PhD*,†

doi: 10.1097/ICO.0000000000002134
Basic Investigation

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.

*Department of Ophthalmology, The Affiliated Second Hospital of Wenzhou Medical University, Wenzhou, China;

Department of Pharmacy, School of Pharmacy, Wenzhou Medical University, Chashan University Park, Wenzhou, China;

Department of Ophthalmology, the Affiliated First Hospital of Wenzhou Medical University, Wenzhou, China;

§Department of molecular biology, College of Life Sciences, Jilin Agricultural University, Changchun, China; and

Department of Ophthalmology, School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, China.

Correspondence: Xiaojie Wang, Wenzhou Medical University, Chashan University Park, Wenzhou 325035, China (e-mail:

This research was funded by the National Health Commission of China (No. 2016ZX09101117), the National Natural Science Foundation of China (No. 81070714 and No. 81601695), the Natural Science Foundation of Zhejiang Province (No. LY17H150002 and No. LY17H300003), and the Wenzhou Science and Technology Bureau (No. Y20150108).

The authors have no conflicts of interest to disclose.

J. Cai, Q. Zhou, and Z. Wang contributed equally to this study.

Received January 31, 2019

Received in revised form July 08, 2019

Accepted July 19, 2019

Online date: August 30, 2019

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