Essential role for c-Jun N-terminal kinase 2 in corneal epithelial response to desiccating stress.
OBJECTIVE
To investigate the protective effects of c-Jun N-terminal kinase (JNK)-1 and -2 gene knockout (KO) on the corneal epithelial response to desiccating stress.


METHODS
The C57BL/6, JNK1KO, and JNK2KO mice were subjected to desiccating stress (DS) for 5 days. The effects of DS on the corneal epithelium were evaluated by measuring corneal smoothness and permeability. Expression of matrix metalloproteinases (MMP)-1, MMP-9, and cornified envelope protein precursors (small proline-rich protein [SPRR]-1a, SPRR-2a, and involucrin) in the corneal epithelia was evaluated by immunostaining and real-time polymerase chain reaction. Collagenase and gelatinase activity in corneal sections as measured with in situ fluorescent assays.


RESULTS
The JNK2KO mice had smoother corneal surfaces and less corneal barrier disruption in response to DS than JNK1KO mice and C57BL/6 wild-type control mice. The DS increased levels of MMP-1, MMP-9, SPRR-1a, SPRR-2a, involucrin immunoreactivity, and mRNA transcripts in the corneal epithelium of JNK1KO and C57BL/6 mice, but not in JNK2KO mice. Knockout of JNK2 prevented DS-induced increase in gelatinase and collagenase activity in the cornea.


CONCLUSIONS
The JNK2 protein appears to have an essential role in desiccation-induced corneal epithelial disease by stimulating production of MMP-1, MMP-9, and cornified envelope precursors. Clinical Relevance The JNK2 protein could be a novel therapeutic target in dry eye disease.
De Paiva
Cintia S
CS
Ocular Surface Center, Cullen Eye Institute, Baylor College of Medicine, 6565 Fannin St, NC 205, Houston, TX 77030, USA. cintiadp@bcm.tmc.edu
Pangelinan
Solherny B
SB
Chang
Emmanuel
E
Yoon
K-C
KC
Farley
William J
WJ
Li
De-Quan
DQ
Pflugfelder
Stephen C
SC
D000818:Animals; D003316:Corneal Diseases / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D055233:Cornified Envelope Proline-Rich Proteins / Q000235:genetics / Q000378:metabolism; D003890:Desiccation; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000201:enzymology* / Q000209:etiology / Q000517:prevention & control*; D019573:Epithelium, Corneal / Q000201:enzymology*; D005456:Fluorescent Dyes / Q000378:metabolism; D015590:Fluorophotometry; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D048055:Mitogen-Activated Protein Kinase 8 / Q000502:physiology; D048056:Mitogen-Activated Protein Kinase 9 / Q000502:physiology*; D009930:Organic Chemicals / Q000378:metabolism; D010539:Permeability; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013312:Stress, Physiological
D055233:Cornified Envelope Proline-Rich Proteins; D005456:Fluorescent Dyes; C403124:Oregon Green BAPTA-dextran; D009930:Organic Chemicals; D011498:Protein Precursors; D012333:RNA, Messenger; C524532:Sprr1a protein, mouse; C491091:Sprr2a1 protein, mouse; C032253:involucrin; D048056:Mitogen-Activated Protein Kinase 9; D048055:Mitogen-Activated Protein Kinase 8; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1