Lacritin and other new proteins of the lacrimal functional unit.
Lacritin and other new proteins of the lacrimal functional unit.
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DOI：
10.1016/j.exer.2008.09.002
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发表时间：
2009-05
影响因子：
3.4
通讯作者：
Laurie, Gordon W.
中科院分区：
文献类型：
--
作者：
McKown, Robert L.;Wang, Ningning;Raab, Ronald W.;Karnati, Roy;Zhang, Yinghui;Williams, Patricia B.;Laurie, Gordon W.
2007年国际干眼研讨会将泪腺功能单位（LFU）定义为“一个综合系统，包括泪腺、眼表面（角膜、结膜和睑板腺）和眼睑，以及连接它们的感觉和运动神经”。 LFU 主要通过功能正常的泪膜维持健康的眼表，为角膜上皮细胞更新提供保护、润滑和环境。 LFU 细胞表达数千种蛋白质。在过去十年中，已经发现了超过 200 种新的 LFU 蛋白。 Lacritin 是人类泪液中的一种新型 LFU 特异性生长因子，可通过导管流向眼表面的角膜上皮细胞。当局部应用于兔子时，泪泌素似乎会增加基础泪液分泌量。泪素是初步报道在睑缘炎和两种干眼综合征中表达下调的少数泪液蛋白之一。计算分析预测了一个有序的 C 末端结构域，该结构域结合角膜上皮细胞表面蛋白聚糖 syndecan-1 (SDC1)，并且是乳泌素的低纳摩尔有丝分裂活性所必需的。 SDC1 N 末端的泪泌素结合位点被乙酰肝素酶暴露。乙酰肝素酶由角膜上皮组成性表达，并且似乎是眼泪的正常成分。结合触发向下游 NFAT 和 mTOR 的快速信号传导。人类 LFU 表达了许多其他新蛋白质，这些蛋白质在首次通过基因组测序鉴定时最初被指定为假设的，包括：ALS2CL、ARHGEF19、KIAA1109、PLXNA1、POLG、WIPI1 和 ZMIZ2。它们在人类遗传疾病或基本细胞功能中所表现或暗示的作用为新的研究提供了动力。用新的 LFU 蛋白解决眼表生理学的局部领域可能会揭示有趣的新生物学机制，并有助于深入了解眼表功能障碍的核心。
The lacrimal functional unit (LFU) is defined by the 2007 International Dry Eye WorkShop as ‘an integrated system comprising the lacrimal glands, ocular surface (cornea, conjunctiva and meibomian glands) and lids, and the sensory and motor nerves that connect them’. The LFU maintains a healthy ocular surface primarily through a properly functioning tear film that provides protection, lubrication, and an environment for corneal epithelial cell renewal. LFU cells express thousands of proteins. Over two hundred new LFU proteins have been discovered in the last decade. Lacritin is a new LFU-specific growth factor in human tears that flows through ducts to target corneal epithelial cells on the ocular surface. When applied topically in rabbits, lacritin appears to increase the volume of basal tear secretion. Lacritin is one of only a handful of tear proteins preliminarily reported to be downregulated in blepharitis and in two dry eye syndromes. Computational analysis predicts an ordered C-terminal domain that binds the corneal epithelial cell surface proteoglycan syndecan-1 (SDC1) and is required for lacritin’s low nanomolar mitogenic activity. The lacritin binding site on the N-terminus of SDC1 is exposed by heparanase. Heparanase is constitutively expressed by the corneal epithelium and appears to be a normal constituent of tears. Binding triggers rapid signaling to downstream NFAT and mTOR. A wealth of other new proteins, originally designated as hypothetical when first identified by genomic sequencing, are expressed by the human LFU including: ALS2CL, ARHGEF19, KIAA1109, PLXNA1, POLG, WIPI1 and ZMIZ2. Their demonstrated or implied roles in human genetic disease or basic cellular functions are fuel for new investigation. Addressing topical areas in ocular surface physiology with new LFU proteins may reveal interesting new biological mechanisms and help get to the heart of ocular surface dysfunction.
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DOI：
10.1083/jcb.138.3.495
发表时间：
1997-08-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chen YG;Siddhanta A;Austin CD;Hammond SM;Sung TC;Frohman MA;Morris AJ;Shields D
通讯作者：
Shields D
影响因子：
5.1
作者：
Chandran, Jayanth;Ding, Jinhui;Cai, Huaibin
通讯作者：
Cai, Huaibin
影响因子：
--
作者：
Huang, CY;Beliakoff, J;Sun, ZJ
通讯作者：
Sun, ZJ
影响因子：
64.5
作者：
Horsley, Valerie;Aliprantis, Antonios O.;Fuchs, Elaine
通讯作者：
Fuchs, Elaine
影响因子：
4.4
作者：
Blalock, Timothy D.;Spurr-Michaud, Sandra J.;Gipson, Ilene K.
通讯作者：
Gipson, Ilene K.