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Low humidity environmental challenge causes barrier disruption and cornification of the mouse corneal epithelium via a c-jun N-terminal kinase 2 (JNK2) pathway.
Exp Eye Res. 2012 Jan; 94(1):150-6.EE

Abstract

Patients with tear dysfunction often experience increased irritation symptoms when subjected to drafty and/or low humidity environmental conditions. The purpose of this study was to investigate the effects of low humidity stress (LHS) on corneal barrier function and expression of cornified envelope (CE) precursor proteins in the epithelium of C57BL/6 and c-jun N-terminal kinase 2 (JNK2) knockout (KO) mice. LHS was induced in both strains by exposure to an air draft for 15 (LHS15D) or 30 days (LHS30D) at a relative humidity <30%RH. Nonstressed (NS) mice were used as controls. Oregon-green-dextran uptake was used to measure corneal barrier function. Levels of small proline-rich protein (SPRR)-2, involucrin, occludin, and MMP-9 were evaluated by immunofluorescent staining in cornea sections. Wholemount corneas immunostained for occludin were used to measure mean apical cell area. Gelatinase activity was evaluated by in situ zymography. Expression of MMP, CE and inflammatory cytokine genes was evaluated by qPCR. C57BL/6 mice exposed to LHS15D showed corneal barrier dysfunction, decreased apical corneal epithelial cell area, higher MMP-9 expression and gelatinase activity and increased involucrin and SPRR-2 immunoreactivity in the corneal epithelium compared to NS mice. JNK2KO mice were resistant to LHS-induced corneal barrier disruption. MMP-3,-9,-13, IL-1α, IL-1β, involucrin and SPRR-2a RNA transcripts were significantly increased in C57BL/6 mice at LHS15D, while no change was noted in JNK2KO mice. LHS is capable of altering corneal barrier function, promoting pathologic alteration of the TJ complex and stimulating production of CE proteins by the corneal epithelium. Activation of the JNK2 signaling pathway contributes to corneal epithelial barrier disruption in LHS.

Authors+Show Affiliations

Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, 6565 Fannin Street, NC 205, Houston, TX, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22166618

Citation

Pelegrino, F S A., et al. "Low Humidity Environmental Challenge Causes Barrier Disruption and Cornification of the Mouse Corneal Epithelium Via a C-jun N-terminal Kinase 2 (JNK2) Pathway." Experimental Eye Research, vol. 94, no. 1, 2012, pp. 150-6.
Pelegrino FS, Pflugfelder SC, De Paiva CS. Low humidity environmental challenge causes barrier disruption and cornification of the mouse corneal epithelium via a c-jun N-terminal kinase 2 (JNK2) pathway. Exp Eye Res. 2012;94(1):150-6.
Pelegrino, F. S., Pflugfelder, S. C., & De Paiva, C. S. (2012). Low humidity environmental challenge causes barrier disruption and cornification of the mouse corneal epithelium via a c-jun N-terminal kinase 2 (JNK2) pathway. Experimental Eye Research, 94(1), 150-6. https://doi.org/10.1016/j.exer.2011.11.022
Pelegrino FS, Pflugfelder SC, De Paiva CS. Low Humidity Environmental Challenge Causes Barrier Disruption and Cornification of the Mouse Corneal Epithelium Via a C-jun N-terminal Kinase 2 (JNK2) Pathway. Exp Eye Res. 2012;94(1):150-6. PubMed PMID: 22166618.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Low humidity environmental challenge causes barrier disruption and cornification of the mouse corneal epithelium via a c-jun N-terminal kinase 2 (JNK2) pathway. AU - Pelegrino,F S A, AU - Pflugfelder,S C, AU - De Paiva,C S, Y1 - 2011/12/07/ PY - 2011/08/26/received PY - 2011/11/05/revised PY - 2011/11/29/accepted PY - 2011/12/15/entrez PY - 2011/12/15/pubmed PY - 2012/3/9/medline SP - 150 EP - 6 JF - Experimental eye research JO - Exp Eye Res VL - 94 IS - 1 N2 - Patients with tear dysfunction often experience increased irritation symptoms when subjected to drafty and/or low humidity environmental conditions. The purpose of this study was to investigate the effects of low humidity stress (LHS) on corneal barrier function and expression of cornified envelope (CE) precursor proteins in the epithelium of C57BL/6 and c-jun N-terminal kinase 2 (JNK2) knockout (KO) mice. LHS was induced in both strains by exposure to an air draft for 15 (LHS15D) or 30 days (LHS30D) at a relative humidity <30%RH. Nonstressed (NS) mice were used as controls. Oregon-green-dextran uptake was used to measure corneal barrier function. Levels of small proline-rich protein (SPRR)-2, involucrin, occludin, and MMP-9 were evaluated by immunofluorescent staining in cornea sections. Wholemount corneas immunostained for occludin were used to measure mean apical cell area. Gelatinase activity was evaluated by in situ zymography. Expression of MMP, CE and inflammatory cytokine genes was evaluated by qPCR. C57BL/6 mice exposed to LHS15D showed corneal barrier dysfunction, decreased apical corneal epithelial cell area, higher MMP-9 expression and gelatinase activity and increased involucrin and SPRR-2 immunoreactivity in the corneal epithelium compared to NS mice. JNK2KO mice were resistant to LHS-induced corneal barrier disruption. MMP-3,-9,-13, IL-1α, IL-1β, involucrin and SPRR-2a RNA transcripts were significantly increased in C57BL/6 mice at LHS15D, while no change was noted in JNK2KO mice. LHS is capable of altering corneal barrier function, promoting pathologic alteration of the TJ complex and stimulating production of CE proteins by the corneal epithelium. Activation of the JNK2 signaling pathway contributes to corneal epithelial barrier disruption in LHS. SN - 1096-0007 UR - https://www.unboundmedicine.com/medline/citation/22166618/Low_humidity_environmental_challenge_causes_barrier_disruption_and_cornification_of_the_mouse_corneal_epithelium_via_a_c_jun_N_terminal_kinase_2__JNK2__pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4835(11)00397-6 DB - PRIME DP - Unbound Medicine ER -