Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
Invest Ophthalmol Vis Sci. 2012 Aug 13;53(9):5416-25. doi: 10.1167/iovs.12-9891.
To investigate the expression, localization, and physiologic function of renin-angiotensin system (RAS) components in the mouse lacrimal gland.
Lacrimal glands and cultured lacrimal gland fibroblasts from wild-type (WT) BALB/c (H-2(d)) mice were used. Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry were used to determine the expression and localization of the RAS components, prorenin/renin, angiotensin-converting enzyme (ACE), angiotensin II, angiotensin II type 1 receptor (AT1R), and angiotensin II type 2 receptor (AT2R) in the normal mouse lacrimal gland. To examine the change in tear secretion, mice received ARB (AT1R blocker) or AT2R antagonist. Tear secretion was assessed by cotton thread test before and after drug administration.
The mRNAs coding for angiotensinogen, prorenin, ACE, and both AT1R and AT2R were found in normal lacrimal gland tissue and cultured lacrimal gland fibroblasts. Prorenin/renin and ACE were identified in myoepithelial cells around ducts and acini and in blood vessels. Angiotensin II, AT1R, and AT2R were observed in the ducts and interstitial fibroblasts. AT1R and AT2R were also localized in blood vessels. All the cultured lacrimal gland fibroblasts expressed angiotensin II, AT1R, and AT2R. Tear secretion increased in mice that received ARB.
The results are consistent with the hypothesis that a tissue-specific RAS is present in the lacrimal gland, and suggest that fibroblasts are one of the cell types playing a role in the tissue RAS. Tissue RAS might be involved in tissue function of regulating tear secretion in the lacrimal gland.
研究肾素-血管紧张素系统(RAS)各成分在小鼠泪腺中的表达、定位和生理功能。
使用野生型(WT)BALB/c(H-2(d))小鼠的泪腺和培养的泪腺成纤维细胞。采用逆转录-聚合酶链反应(RT-PCR)和免疫组织化学方法,检测 RAS 各成分前体肾素/肾素、血管紧张素转换酶(ACE)、血管紧张素 II、血管紧张素 II 型 1 受体(AT1R)和血管紧张素 II 型 2 受体(AT2R)在正常小鼠泪腺中的表达和定位。为了检测泪液分泌的变化,小鼠接受了 ARB(AT1R 阻滞剂)或 AT2R 拮抗剂。给药前后,通过棉线试验评估泪液分泌。
在正常泪腺组织和培养的泪腺成纤维细胞中均发现编码血管紧张素原、前体肾素、ACE 以及 AT1R 和 AT2R 的 mRNA。前体肾素/肾素和 ACE 被鉴定为在导管和腺泡周围的肌上皮细胞以及血管中存在。血管紧张素 II、AT1R 和 AT2R 存在于导管和间质成纤维细胞中。AT1R 和 AT2R 也定位于血管中。所有培养的泪腺成纤维细胞均表达血管紧张素 II、AT1R 和 AT2R。接受 ARB 的小鼠泪液分泌增加。
这些结果与假设即组织特异性 RAS 存在于泪腺中一致,并提示成纤维细胞是参与组织 RAS 的细胞类型之一。组织 RAS 可能参与调节泪液分泌的组织功能。