Aquaporin gene therapy corrects Sjogren's syndrome phenotype in mice
Aquaporin gene therapy corrects Sjogren's syndrome phenotype in mice
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DOI：
10.1073/pnas.1601992113
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发表时间：
2016-05-17
影响因子：
11.1
通讯作者：
Chiorini, John A.
中科院分区：
文献类型：
--
作者：
Lai, Zhennan;Yin, Hongen;Chiorini, John A.
原发性干燥综合征（pSS）是一种慢性自身免疫性疾病，估计影响全球3500万人。目前，对于干燥综合征没有有效的治疗方法，并且对与口干症和唾液分泌不足相关的生理机制的理解有限。目前的工作表明，水通道蛋白5的表达，唾液腺液体分泌的关键水通道，是由骨形态发生蛋白6。这种细胞因子的表达增加与原发性干燥综合征的最常见症状，唾液腺功能丧失密切相关。这一发现使我们开发了一种治疗干燥综合征的疗法，通过增加腺体的水渗透性来恢复唾液流动。我们的研究表明，有针对性地增加腺体渗透性不仅导致分泌腺功能的恢复，而且还解决了与疾病相关的标志性唾液腺炎症和全身炎症。泪腺分泌功能也增加，表明这种局部治疗可以治疗与原发性干燥综合征相关的全身症状。
Primary Sjogren's syndrome (pSS) is a chronic autoimmune disease that is estimated to affect 35 million people worldwide. Currently, no effective treatments exist for Sjogren's syndrome, and there is a limited understanding of the physiological mechanisms associated with xerostomia and hyposalivation. The present work revealed that aquaporin 5 expression, a water channel critical for salivary gland fluid secretion, is regulated by bone morphogenetic protein 6. Increased expression of this cytokine is strongly associated with the most common symptom of primary Sjogren's syndrome, the loss of salivary gland function. This finding led us to develop a therapy in the treatment of Sjogren's syndrome by increasing the water permeability of the gland to restore saliva flow. Our study demonstrates that the targeted increase of gland permeability not only resulted in the restoration of secretory gland function but also resolved the hallmark salivary gland inflammation and systemic inflammation associated with disease. Secretory function also increased in the lacrimal gland, suggesting this local therapy could treat the systemic symptoms associated with primary Sjogren's syndrome.