Defective cellular trafficking of lacrimal gland aquaporin-5 in Sjögren's syndrome

Tsubota, Kazuo; Hirai, Shinichiro; King, Landon S.; Agre, Peter; Ishida, Narihiro

doi:10.1016/s0140-6736(00)04140-4

Cited by 234 publications

(165 citation statements)

References 4 publications

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“…In other epithelia, where areanormalized rates of fluid absorption/secretion are much lower, AQPs are not required for transepithelial fluid transport, as found for tear fluid secretion by lacrimal gland , sweat secretion (Song et al, 2002), alveolar fluid absorption (Bai et al, 1999;, and airway fluid absorption . Involvement of AQP-in the reduced tear fluid secretion in Sjogren's syndrome has been suggested (Tsubota et al, 2001), though subsequently refuted (Beroukas et al, 2001). AQPs and lacrimal gland function will not be discussed further based on the negative phenotype from our lab and others Sasaki et al, 2007).…”

Section: Aqp Roles Related To Aqp-facilitated Water Transportmentioning

confidence: 94%

Functions of aquaporins in the eye

Verkman

Ruiz-Ederra

Levin

2008

Progress in Retinal and Eye Research

171

117

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The aquaporins (AQPs) are integral membrane proteins whose main function is to transport water across cell membranes in response to osmotic gradients. At the ocular surface, AQP1 is expressed in corneal endothelium, AQP3 and AQP5 in corneal epithelium, and AQP3 in conjunctival epithelium. AQPs are also expressed in lens fiber cells (AQP0), lens epithelium (AQP1), ciliary epithelium (AQP1, AQP4) and retinal Müller cells (AQP4). Mutations in AQP0 produce congenital cataracts in humans. Analysis of knockout mice lacking individual AQPs suggests their involvement in maintenance of corneal and lens transparency, corneal epithelial repair, intraocular pressure regulation, retinal signal transduction and retinal swelling following injury. The mouse phenotype findings implicate AQPs as potential drug targets for therapy of elevated intraocular pressure and ocular disorders involving the cornea, lens and retina. However, much research remains in defining cell-level mechanisms for the ocular AQP functions, in establishing the relevance to human eye disease of conclusions from knockout mice, and in developing AQPmodulating drugs.

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Section: Aqp Roles Related To Aqp-facilitated Water Transportmentioning

confidence: 94%

Functions of aquaporins in the eye

Verkman

Ruiz-Ederra

Levin

2008

Progress in Retinal and Eye Research

171

117

View full text Add to dashboard Cite

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“…Consequently, the increased UWS flow seen following IFN alfa treatment may be due to an upregulation of AQP5, with highly selective water channel proteins reported to be abnormally distributed in lacrimal and salivary glands of Sjö gren's syndrome patients (35,36).…”

Section: Cummins Et Almentioning

confidence: 99%

Treatment of primary sjögren's syndrome with low‐dose human interferon alfa administered by the oromucosal route: Combined phase III results

Cummins

Papas

Kammer

et al. 2003

Arthritis & Rheumatism

123

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Objective. This study tested the safety and efficacy of human interferon (IFN) alfa for treatment of salivary hypofunction and dry mouth symptoms in primary Sjö gren's syndrome patients. Methods. Combined results are reported from 2 phase III clinical trials in which a total of 497 subjects with primary Sjö gren's syndrome received 150 international units of human IFN alfa or matching placebo 3 times per day for 24 weeks by the oromucosal route. Results. Subjects given IFN alfa had a significantly (P ‫؍‬ 0.01) greater mean increase in unstimulated whole saliva (UWS) flow, compared with subjects given placebo. In IFN alfa patients, increases in UWS correlated positively and significantly with improvements noted in 7 of 8 symptoms associated with oral and ocular dryness. The coprimary endpoints of stimulated whole saliva flow and oral dryness were not significantly improved in the IFN alfa group relative to placebo. No significant differences were found between the groups with respect to overall adverse event incidence or severity. Conclusion. IFN alfa given at low dosage by the oromucosal route can significantly increase UWS flow in patients with primary Sjö gren's syndrome, without causing significant adverse events.

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“…The N-terminal and C-terminal halves are sequence-related, and loop B and E each contain the Asn-Pro-Ala (NPA) motif seen in the other aquaporins [3]. However, the cytoplasmic loop D contains a cAMP-protein kinase phosphorylation consensus site (Ser-Arg-Arg-Thr-Ser) which is seen only in AQP2 [3][4][5]. In normal tissues, AQP5 is expressed strongly in the salivary glands and the eye but expression is also seen in the lacrimal gland, trachea, and lung [3].…”

Section: Introductionmentioning

confidence: 99%

“…In normal tissues, AQP5 is expressed strongly in the salivary glands and the eye but expression is also seen in the lacrimal gland, trachea, and lung [3]. Furthermore, examination of the distribution of AQP5 in lacrimal gland determined that a selective defect in the trafficking of AQP5 in the lacrimal gland may contribute to the pathogenesis of Sjogren syndrome [5].…”

Section: Introductionmentioning

confidence: 99%

Overexpression of AQP5, a putative oncogene, promotes cell growth and transformation

et al. 2008

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Overexpression of several aquaporins has been reported in different types of human cancer but the role of AQPs in human carcinogenesis has not yet been clearly defined. Here, we demonstrate that ectopic expression of human AQP5 (hAQP5), a water channel expressed in lung, salivary glands, and kidney, induces many phenotypic changes characteristic of transformation both in vitro and in vivo. Furthermore, the cell proliferative ability of AQP5 appears to be dependent upon the phosphorylation of a cAMP-protein kinase (PKA) consensus site located in a cytoplasmic loop of AQP5. In addition, phosphorylation of the PKA consensus site was found to be phosphorylated preferentially in tumors. These findings altogether indicate that hAQP5 plays an important role in human carcinogenesis and, furthermore, provide an attractive therapeutic target.

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Defective cellular trafficking of lacrimal gland aquaporin-5 in Sjögren's syndrome

Cited by 234 publications

References 4 publications

Functions of aquaporins in the eye

Functions of aquaporins in the eye

Treatment of primary sjögren's syndrome with low‐dose human interferon alfa administered by the oromucosal route: Combined phase III results

Overexpression of AQP5, a putative oncogene, promotes cell growth and transformation

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