|Hyperosmolarity-induced cornification of human corneal epithelial cells is regulated by JNK MAPK|
|Chen, Zhuo1; Tong, Louis1,4; Li, Zhijie2; Yoon, Kyung-Chul1,3; Qi, Hong1,5; Farley, William1; Li, De-Quan1; Pflugfelder, Stephen C.1|
|刊名||INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE|
|收录类别||ISTP ; SCI|
|WOS标题词||Science & Technology|
|关键词[WOS]||EXPANDED EX-VIVO ; DRY-EYE ; CORNIFIED ENVELOPE ; OCULAR SURFACE ; APOPTOSIS ; TRANSGLUTAMINASE ; PROLIFERATION ; EXPRESSION ; GROWTH ; DEATH|
PURPOSE. To evaluate the effects of hyperosmolar stress on expression of cornified envelope (CE) precursors and transglutaminases (TGs) by primary cultured human corneal epithelial (PCHCE) cells and the regulatory effects of JNK MAPK on this process.
METHODS. Expression of CE precursors and TGs were evaluated in PCHCE cells exposed to media of increasing osmolarity (350-450 mOsM) for 24, 48, and 72 hours. JNK1 and -2 MAPKs were inhibited by addition of short interfering (si) RNA. Relative levels of mRNA transcripts and proteins were evaluated. TG activity, cell viability, and apoptosis were detected in PCHCE cells, with or without siRNA-JNKs.
RESULTS. Exposure of PCHCE cells to hyperosmolar medium increased TG activity at 3 hours, levels of the CE precursors SPRR1b and -2a and membrane-associated TG1 mRNA at 6 hours, and tissue-type TG2 mRNA at 24 hours. Osmotic stress decreased corneal epithelial cell viability, which was due in part to stimulation of apoptosis and cornification death. Inhibiting JNK2 production by siRNA in osmotically stressed PCHCE cells prevented the stimulation of SPRR and membrane-associated TG1 production and TG activity, and improved cell viability, whereas inhibition of JNK1 prevented early apoptosis.
CONCLUSIONS. Osmotic stress promotes production of certain CE proteins and cross-linking membrane-associated TG1 and decreases cell viability via JNK MAPK-mediated pathways. Strategies that inhibit JNK production downregulate the cornification response of PCHCE cells to osmotic stress. These findings have potential therapeutic implications for preventing cornification of the corneal epithelium in response to the hyperosmolar tear film in dry eye disease.
|作者单位||1.Baylor Coll Med, Cullen Eye Inst, Dept Ophthalmol, Ocular Surface Ctr, Houston, TX 77030 USA|
2.Baylor Coll Med, Leukocyte Biol Sect, Dept Pediat, Houston, TX 77030 USA
3.Chonnam Natl Univ, Dept Ophthalmol, Sch Med, Kwangju, South Korea
4.Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore
5.Peking Univ, Hosp 3, Peking Univ Eye Ctr, Beijing 100871, Peoples R China
|Chen, Zhuo,Tong, Louis,Li, Zhijie,et al. Hyperosmolarity-induced cornification of human corneal epithelial cells is regulated by JNK MAPK[J]. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE,2008,49(2):539-549.|
|APA||Chen, Zhuo.,Tong, Louis.,Li, Zhijie.,Yoon, Kyung-Chul.,Qi, Hong.,...&Pflugfelder, Stephen C..(2008).Hyperosmolarity-induced cornification of human corneal epithelial cells is regulated by JNK MAPK.INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE,49(2),539-549.|
|MLA||Chen, Zhuo,et al."Hyperosmolarity-induced cornification of human corneal epithelial cells is regulated by JNK MAPK".INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 49.2(2008):539-549.|