NDLI: Essential Role for c-Jun N-Terminal Kinase 2 in Corneal Epithelial Response to Desiccating Stress

Content Provider	JAMA Network
Author	Paiva, Cintia S. De Pangelinan, Solherny B. Chang, Emmanuel Yoon, K.-C. Farley, William J. Li, De-Quan Pflugfelder, Stephen C.
Copyright Year	2009
Abstract	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 m: RNA 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. Conclusion: 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.
Ending Page	1631
Starting Page	1625
Page Count	7
File Format	PDF HTM / HTML
ISSN	00039950
DOI	10.1001/archophthalmol.2009.316
Issue Number	12
Journal	Archives of Ophthalmology
Volume Number	127
Language	English
Publisher	American Medical Association
Publisher Date	2009-12-14
Access Restriction	Open
Subject Keyword	epithelium collagenase phosphotransferases cornea stress dry eye syndromes gelatinase b gelatinases desiccation interstitial collagenase cornified envelope matrix metalloproteinases inbred c57bl mice polymerase chain reaction mice permeability corneal epithelium
Content Type	Text
Resource Type	Article
Subject	Ophthalmology

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