PMID- 31490279 OWN - NLM STAT- MEDLINE DCOM- 20200302 LR - 20200302 IS - 1536-4798 (Electronic) IS - 0277-3740 (Linking) VI - 38 IP - 11 DP - 2019 Nov TI - Comparative Analysis of KGF-2 and bFGF in Prevention of Excessive Wound Healing and Scar Formation in a Corneal Alkali Burn Model. PG - 1430-1437 LID - 10.1097/ICO.0000000000002134 [doi] AB - 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 alpha-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. FAU - Cai, JianQiu AU - Cai J AD - Department of Ophthalmology, The Affiliated Second Hospital of Wenzhou Medical University, Wenzhou, China. AD - Department of Pharmacy, School of Pharmacy, Wenzhou Medical University, Chashan University Park, Wenzhou, China. FAU - Zhou, Qingde AU - Zhou Q AD - Department of Pharmacy, School of Pharmacy, Wenzhou Medical University, Chashan University Park, Wenzhou, China. FAU - Wang, Zhitao AU - Wang Z AD - Department of Pharmacy, School of Pharmacy, Wenzhou Medical University, Chashan University Park, Wenzhou, China. FAU - Guo, Ruide AU - Guo R AD - Department of Ophthalmology, the Affiliated First Hospital of Wenzhou Medical University, Wenzhou, China. FAU - Yang, Rongshuai AU - Yang R AD - Department of Pharmacy, School of Pharmacy, Wenzhou Medical University, Chashan University Park, Wenzhou, China. FAU - Yang, Xuanxin AU - Yang X AD - Department of Pharmacy, School of Pharmacy, Wenzhou Medical University, Chashan University Park, Wenzhou, China. FAU - Li, Wenqing AU - Li W AD - Department of Pharmacy, School of Pharmacy, Wenzhou Medical University, Chashan University Park, Wenzhou, China. FAU - Ahmad, Naveed AU - Ahmad N AD - Department of molecular biology, College of Life Sciences, Jilin Agricultural University, Changchun, China. FAU - Chen, Qi AU - Chen Q AD - Department of Pharmacy, School of Pharmacy, Wenzhou Medical University, Chashan University Park, Wenzhou, China. AD - Department of Ophthalmology, School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Hui, Qi AU - Hui Q AD - Department of Ophthalmology, The Affiliated Second Hospital of Wenzhou Medical University, Wenzhou, China. AD - Department of Pharmacy, School of Pharmacy, Wenzhou Medical University, Chashan University Park, Wenzhou, China. FAU - Wang, Xiaojie AU - Wang X AD - Department of Ophthalmology, The Affiliated Second Hospital of Wenzhou Medical University, Wenzhou, China. AD - Department of Pharmacy, School of Pharmacy, Wenzhou Medical University, Chashan University Park, Wenzhou, China. LA - eng PT - Comparative Study PT - Journal Article PL - United States TA - Cornea JT - Cornea JID - 8216186 RN - 0 (Alkalies) RN - 0 (Fibroblast Growth Factor 10) RN - 103107-01-3 (Fibroblast Growth Factor 2) SB - IM MH - Alkalies/toxicity MH - Animals MH - Burns, Chemical/complications/*drug therapy/pathology MH - Cell Movement/drug effects MH - Cell Proliferation/drug effects MH - Cells, Cultured MH - Cornea/drug effects/pathology MH - Corneal Injuries/complications/*drug therapy/pathology MH - Disease Models, Animal MH - Eye Burns/complications/*drug therapy/pathology MH - Fibroblast Growth Factor 10/*pharmacology MH - Fibroblast Growth Factor 2/*pharmacology MH - Keloid/etiology/pathology/*prevention & control MH - Microscopy, Acoustic MH - Rats MH - Wound Healing/*drug effects EDAT- 2019/09/07 06:00 MHDA- 2020/03/03 06:00 CRDT- 2019/09/07 06:00 PHST- 2019/09/07 06:00 [pubmed] PHST- 2020/03/03 06:00 [medline] PHST- 2019/09/07 06:00 [entrez] AID - 10.1097/ICO.0000000000002134 [doi] PST - ppublish SO - Cornea. 2019 Nov;38(11):1430-1437. doi: 10.1097/ICO.0000000000002134.