Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, Denmark.
Department of Bioscience, Biotechnologies and Environment, University of Bari, 70125 Bari, Italy.
Cells. 2023 Apr 12;12(8):1140. doi: 10.3390/cells12081140.
Sex hormones play an important role in the regulation of water homeostasis, and we have previously shown that tamoxifen (TAM), a selective estrogen receptor modulator (SERM), affects the regulation of aquaporin (AQP)-2. In this study, we investigated the effect of TAM on the expression and localization of AQP3 in collecting ducts using various animal, tissue, and cell models. The impact of TAM on AQP3 regulation was studied in rats subjected to 7 days of unilateral ureteral obstruction (UUO), with the rats fed a lithium-containing diet to induce nephrogenic diabetes insipidus (NDI), as well as in human precision-cut kidney slices (PCKS). Moreover, intracellular trafficking of AQP3 after TAM treatment was investigated in Madin-Darby Canine Kidney (MDCK) cells stably expressing AQP3. In all models, the expression of AQP3 was evaluated by Western blotting, immunohistochemistry and qPCR. TAM administration attenuated UUO-induced downregulation of AQP3 and affected the localization of AQP3 in both the UUO model and the lithium-induced NDI model. In parallel, TAM also affected the expression profile of other basolateral proteins, including AQP4 and Na/K-ATPase. In addition, TGF-β and TGF-β+TAM treatment affected the localization of AQP3 in stably transfected MDCK cells, and TAM partly attenuated the reduced AQP3 expression in TGF-β exposed human tissue slices. These findings suggest that TAM attenuates the downregulation of AQP3 in a UUO model and a lithium-induced NDI model and affects the intracellular localization in the collecting ducts.
性激素在水稳态调节中发挥重要作用，我们之前已经表明，他莫昔芬（TAM），一种选择性雌激素受体调节剂（SERM），影响水通道蛋白（AQP）-2 的调节。在这项研究中，我们使用各种动物、组织和细胞模型研究了 TAM 对集合管中 AQP3 表达和定位的影响。我们在接受 7 天单侧输尿管梗阻（UUO）的大鼠以及给予含锂饮食以诱导肾性尿崩症（NDI）的大鼠中研究了 TAM 对 AQP3 调节的影响，以及在人精确切割肾切片（PCKS）中。此外，我们还在稳定表达 AQP3 的 Madin-Darby Canine Kidney（MDCK）细胞中研究了 TAM 处理后 AQP3 的细胞内转运。在所有模型中，通过 Western blot、免疫组织化学和 qPCR 评估 AQP3 的表达。TAM 给药减弱了 UUO 诱导的 AQP3 下调，并影响了 AQP3 在 UUO 模型和锂诱导的 NDI 模型中的定位。同时，TAM 还影响了其他基底外侧蛋白的表达谱，包括 AQP4 和 Na/K-ATPase。此外，TGF-β 和 TGF-β+TAM 处理影响了稳定转染的 MDCK 细胞中 AQP3 的定位，TAM 部分减弱了 TGF-β 暴露的人组织切片中 AQP3 表达的减少。这些发现表明，TAM 减弱了 UUO 模型和锂诱导的 NDI 模型中 AQP3 的下调，并影响了集合管中的细胞内定位。
