De Paiva Cintia S, Pangelinan Solherny B, Chang Emmanuel, Yoon K-C, Farley William J, Li De-Quan, Pflugfelder Stephen C
Ocular Surface Center, Cullen Eye Institute, Baylor College of Medicine, 6565 Fannin St, NC 205, Houston, TX 77030, USA.
Arch Ophthalmol. 2009 Dec;127(12):1625-31. doi: 10.1001/archophthalmol.2009.316.
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.
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.
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.
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.
研究c-Jun氨基末端激酶（JNK）-1和-2基因敲除（KO）对角膜上皮应对干燥应激反应的保护作用。
将C57BL/6、JNK1KO和JNK2KO小鼠进行5天的干燥应激（DS）处理。通过测量角膜光滑度和通透性来评估DS对角膜上皮的影响。通过免疫染色和实时聚合酶链反应评估角膜上皮中基质金属蛋白酶（MMP）-1、MMP-9和角质化包膜蛋白前体（富含脯氨酸的小分子蛋白[SPRR]-1a、SPRR-2a和内披蛋白）的表达。用原位荧光测定法测量角膜切片中的胶原酶和明胶酶活性。
与JNK1KO小鼠和C57BL/6野生型对照小鼠相比，JNK2KO小鼠在应对DS时角膜表面更光滑，角膜屏障破坏更少。DS增加了JNK1KO和C57BL/6小鼠角膜上皮中MMP-1、MMP-9、SPRR-1a、SPRR-2a、内披蛋白免疫反应性和mRNA转录本的水平，但在JNK2KO小鼠中未增加。敲除JNK2可防止DS诱导的角膜中明胶酶和胶原酶活性增加。
JNK2蛋白似乎通过刺激MMP-1、MMP-9和角质化包膜前体的产生，在干燥诱导的角膜上皮疾病中起重要作用。临床意义JNK2蛋白可能是干眼症的一个新的治疗靶点。
