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Updated: Jan 26, 2026
An Epithelial Abrasion Model for Studying Corneal Wound Healing
Published on: December 29, 2021
Phosphorylation of MAP kinase in corneal epithelial cells during wound healing
Masaki Imayasu1, Shoichi Shimada
1Department of Anatomy, Nagoya City University Medical School, Nagoya, Japan. imayasu-m@menicon-net.co.jp
Purpose:
To investigate the role of mitogen-activated protein kinase (MAPK), such as p44/42 MAPK, p38 MAPK and stress-activated protein kinase (SAPK), in corneal epithelial cells during the wound healing process.
Methods:
A single non-penetrating incision was produced on rat cornea. Then the corneal wound healing process was observed with an immunocytochemical technique using specific antibodies reacting only with phosphorylated p44/42 MAPK, p38 MAPK or SAPK. Cell lysates of corneal epithelial cells in rabbits stimulated with keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF) were processed for Western blot using antibodies to phosphorylated p44/42 MAPK.
Results:
Maximum activation of p44/42 MAPK was observed in wing and basal cells at wounded regions in rat cornea at 1 hour after the incision. Activation of p44/42 MAPK was still detected in all basal and wing cells at wounded regions at up to 24 hours when the incisions were completely closed, and then receded to normal intensity after 7 days. Neither p38 MAPK nor SAPK were activated during the wound healing process. Western blot analysis of cultured corneal epithelial cells in rabbits showed phosphorylation of p44/42 MAPK after 30 minutes in response to KGF and HGF, whereas non-activated p44/42 MAPK was ordinarily detected even at the absence of KGF or HGF.
Conclusions:
These results demonstrate that p44/42 MAPK is activated during the corneal wound healing process and suggest that KGF and HGF play an important role in initiation of cell migration and proliferation in the initial wound healing process by activating p44/42 MAPK.
Insights
Mitogen-activated protein kinase (MAPK) p44/42 is activated in corneal epithelial cells during wound healing. Growth factors keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF) initiate this process by activating p44/42 MAPK.
Area of Science:
- Ophthalmology
- Cell Biology
- Molecular Biology
Background:
- Corneal wound healing is a complex process involving epithelial cell migration and proliferation.
- Mitogen-activated protein kinases (MAPKs) are key signaling molecules involved in cellular responses to stimuli.
- Specific MAPK pathways, including p44/42 MAPK, p38 MAPK, and SAPK, are investigated for their roles in corneal repair.
Purpose of the Study:
- To investigate the role of specific mitogen-activated protein kinases (MAPKs), namely p44/42 MAPK, p38 MAPK, and stress-activated protein kinase (SAPK), in corneal epithelial cells during the wound healing process.
- To determine the involvement of growth factors like keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF) in activating these MAPK pathways.
Main Methods:
- Induction of a non-penetrating incision in rat corneas to model wound healing.
- Immunocytochemical analysis using specific antibodies to detect phosphorylated forms of p44/42 MAPK, p38 MAPK, and SAPK in corneal tissues.
- Western blot analysis of rabbit corneal epithelial cells stimulated with KGF and HGF to assess p44/42 MAPK phosphorylation.
Main Results:
- p44/42 MAPK showed maximum activation in corneal epithelial cells at wounded sites within 1 hour post-incision, persisting up to 24 hours.
- Activation of p44/42 MAPK was observed in basal and wing cells throughout the wound closure period.
- Neither p38 MAPK nor SAPK were activated during the corneal wound healing process; however, KGF and HGF stimulated p44/42 MAPK phosphorylation in cultured cells.
Conclusions:
- p44/42 MAPK is significantly activated during corneal epithelial wound healing.
- Keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF) play a crucial role in initiating corneal wound healing by activating the p44/42 MAPK pathway.
- The findings suggest that p44/42 MAPK activation is essential for cell migration and proliferation during the early stages of corneal repair.
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