TY - JOUR
T1 - Eph signaling is regulated by miRNA-210
T2 - Implications for corneal epithelial repair
AU - Kaplan, Nihal
AU - Liu, Min
AU - Wang, Junyi
AU - Yang, Wending
AU - Fiolek, Elaina
AU - Peng, Han
AU - Lavker, Robert M.
N1 - Funding Information:
The NU‐SBDRC Skin Tissue Engineering and Morphology Core facility assisted in morphologic analysis. The NU‐SBDRC Is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases Grant AR075049. Imaging work was performed at the Northwestern University Center for Advanced Microscopy generously supported by NCI CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center. High content imaging was performed on the Nikon Biostation CT system purchased with the support of NIH 1S10OD021704 ‐01. This research is supported by National Institutes of Health Grants EY028560 and EY019463 (to R.M.L.), and EY032922 (to H.P.); a Dermatology Foundation research grant and Career Development Award (to H.P.); and an Eversight research grant (to H.P.).
Funding Information:
The NU-SBDRC Skin Tissue Engineering and Morphology Core facility assisted in morphologic analysis. The NU-SBDRC Is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases Grant AR075049. Imaging work was performed at the Northwestern University Center for Advanced Microscopy generously supported by NCI CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center. High content imaging was performed on the Nikon Biostation CT system purchased with the support of NIH 1S10OD021704 -01. This research is supported by National Institutes of Health Grants EY028560 and EY019463 (to R.M.L.), and EY032922 (to H.P.); a Dermatology Foundation research grant and Career Development Award (to H.P.); and an Eversight research grant (to H.P.).
Publisher Copyright:
© 2021 Federation of American Societies for Experimental Biology
PY - 2022/1
Y1 - 2022/1
N2 - A distinct boundary exists between the progenitor cells in the basal limbal epithelium and the more differentiated corneal epithelial basal cells. We have shown that reciprocal expression patterns of EphA2 and Ephrin-A1 are likely to contribute to normal limbal-corneal epithelial compartmentalization as well as play a role in response to injury. How this signaling axis is regulated remains unclear. We have demonstrated that microRNAs (miRNAs) play critical roles in corneal epithelial wound healing and several miRNAs (e.g. miR-210) have been predicted to target ephrins. Previous expression profiling experiments demonstrated that miR-210 is prominently expressed in corneal epithelial cells. RNA-seq data acquired from miR-210-depleted HCECs showed up-regulation of genes involved in cellular migration. In addition, miR-210 is decreased after corneal injury while EphA2 is increased. Moreover, antago-210-treated HCECs markedly enhanced wound closure in a scratch wound assay. Antago-210 treatment resulted in increased EphA2 protein levels as well as pS897-EphA2, the pro-migratory form of EphA2. As expected, Ephrin-A1 levels were reduced, while levels of a well-known target of miR-210, Ephrin-A3, were increased by antago-210 treatment. The increase in migration with antago-210 could be inhibited by Ephrin-A1 overexpression, Ephrin-A1-Fc treatment or siRNA depletion of EphA2. However, depletion of Ephrin-A3 did not have effects on the antago-210-induced increase in migration. In addition, Ephrin-A1 overexpression and siEphA2 dampened EGFR signaling, which is increased by antago-210. Our data clearly demonstrate a link between miR-210 and EphA2/Ephrin-A1 signaling that regulates, in part, corneal epithelial migration. This interaction might potentially control the limbal-corneal epithelial boundary.
AB - A distinct boundary exists between the progenitor cells in the basal limbal epithelium and the more differentiated corneal epithelial basal cells. We have shown that reciprocal expression patterns of EphA2 and Ephrin-A1 are likely to contribute to normal limbal-corneal epithelial compartmentalization as well as play a role in response to injury. How this signaling axis is regulated remains unclear. We have demonstrated that microRNAs (miRNAs) play critical roles in corneal epithelial wound healing and several miRNAs (e.g. miR-210) have been predicted to target ephrins. Previous expression profiling experiments demonstrated that miR-210 is prominently expressed in corneal epithelial cells. RNA-seq data acquired from miR-210-depleted HCECs showed up-regulation of genes involved in cellular migration. In addition, miR-210 is decreased after corneal injury while EphA2 is increased. Moreover, antago-210-treated HCECs markedly enhanced wound closure in a scratch wound assay. Antago-210 treatment resulted in increased EphA2 protein levels as well as pS897-EphA2, the pro-migratory form of EphA2. As expected, Ephrin-A1 levels were reduced, while levels of a well-known target of miR-210, Ephrin-A3, were increased by antago-210 treatment. The increase in migration with antago-210 could be inhibited by Ephrin-A1 overexpression, Ephrin-A1-Fc treatment or siRNA depletion of EphA2. However, depletion of Ephrin-A3 did not have effects on the antago-210-induced increase in migration. In addition, Ephrin-A1 overexpression and siEphA2 dampened EGFR signaling, which is increased by antago-210. Our data clearly demonstrate a link between miR-210 and EphA2/Ephrin-A1 signaling that regulates, in part, corneal epithelial migration. This interaction might potentially control the limbal-corneal epithelial boundary.
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UR - http://www.scopus.com/inward/citedby.url?scp=85122041221&partnerID=8YFLogxK
U2 - 10.1096/fj.202101423R
DO - 10.1096/fj.202101423R
M3 - Article
C2 - 34856019
AN - SCOPUS:85122041221
SN - 0892-6638
VL - 36
JO - FASEB Journal
JF - FASEB Journal
IS - 1
M1 - e22076
ER -