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K. Terai, S. Saika, J. Yamada, S. Kinoshita, W. Kao; The Role of TGF-ß and Activin Signals in Corneal Epithelium Wound Healing in Organ Culture Experiment. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3498.
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© ARVO (1962-2015); The Authors (2016-present)
We previously reported that healing of epithelium debridement was delayed in mouse cornea epithelium lacking TGF-ß type II receptor by conditional knock-out, due to inhibition of cell migration suppression albeit an up-regulation of cell proliferation. Additionally, our results suggest that p38MAPK activation by signals from activin receptor can cause wound healing. The purpose of this experiment is to determine the role of activin signals in corneal epithelial wound healing by using organ culture system.
4-week-old C57/BL6 mice were anesthetized and corneal epithelial debridement (2 mm diameter) was created and euthanized. The injured eyes were enucleated immediately and cultured in DMEM supplemented with fetal bovine serum 2.0% as control (1) and with TGF-ß receptor1 (Tbr1) kinase inhibitor (2), follistatin (as activin receptor inhibitor) (3), Tbr1 kinase inhibitor and follistatin (4), SB431542 (as TGF-ß and activin inhibitor) (5), and Tbr1 kinase inhibitor and SB431542 (6). At 12, 24, 48, 72 hrs after debridement, eyes were observed by fluorescein staining and wound areas were measured.
Addition of Tbr1 kinase inhibitor delayed healing of corneal epithelial debridement. However, administration of follistatin did not affected the rate of re-epithelialization following debridement or augment delayed healing caused by Tbr1 kinase inhibitor. Corneal epithelial wound healing delayed by SB431542 but the effect was lower than by Tbr1 kinase inhibitor. The effect of combination of Tbr1 kinase inhibitor and SB431542 was similar as single administration of Tbr1 kinase inhibitor.
These observations are consistent with the notion that Tbr1 kinase inhibitor is not specific for TGF-ß signaling and it may also inhibits activin signaling similar to SB431542. It is observed in this organ culture corneal epithelium wound healing model that inhibition of both TGF-ß signaling and activin signaling causes healing delay. Inhibition of activin signaling does not perturb corneal epithelial wound healing, is consistent with the assumption that the activin signaling does not play a pivotal role in corneal epithelial wound healing when TGF-ß signaling is functional. The function of activin signaling in absence of TGF-ß signaling is still unclear, further investigation is needed to elucidate its role on wound healing in the absence of TGF-ß signaling.
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