Forman Katherine, Martínez Fernando, Cifuentes Manuel, Bertinat Romina, Salazar Katterine, Nualart Francisco
Centro de Microscopía Avanzada, CMA BIO BIO, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción, Chile.
Departamento de Nutrición y Dietética, Facultad de Farmacia, Universidad de Concepción, Concepción, Chile.
J Cell Physiol. 2017 Sep;232(9):2418-2426. doi: 10.1002/jcp.25504. Epub 2017 Mar 24.
In the kidney, vitamin C is reabsorbed from the glomerular ultrafiltrate by sodium-vitamin C cotransporter isoform 1 (SVCT1) located in the brush border membrane of the proximal tubules. Although we know that vitamin C levels decrease with age, the adaptive physiological mechanisms used by the kidney for vitamin C reabsorption during aging remain unknown. In this study, we used an animal model of accelerated senescence (SAMP8 mice) to define the morphological alterations and aging-induced changes in the expression of vitamin C transporters in renal tissue. Aging induced significant morphological changes, such as periglomerular lymphocytic infiltrate and glomerular congestion, in the kidneys of SAMP8 mice, although no increase in collagen deposits was observed using 2-photon microscopy analysis and second harmonic generation. The most characteristic histological alteration was the dilation of intracellular spaces in the basolateral region of proximal tubule epithelial cells. Furthermore, a combination of laser microdissection, qRT-PCR, and immunohistochemical analyses allowed us to determine that SVCT1 expression specifically increased in the proximal tubules from the outer strip of the outer medulla (segment S3) and cortex (segment S2) during aging and that these tubules also express GLUT1. We conclude that aging modulates vitamin C transporter expression and that renal over-expression of SVCT1 enhances vitamin C reabsorption in aged animals that may synthesize less vitamin C. J. Cell. Physiol. 232: 2418-2426, 2017. © 2016 Wiley Periodicals, Inc.
在肾脏中,维生素C通过位于近端小管刷状缘膜的钠-维生素C共转运体亚型1(SVCT1)从肾小球超滤液中重吸收。尽管我们知道维生素C水平会随着年龄增长而降低,但肾脏在衰老过程中用于维生素C重吸收的适应性生理机制仍然未知。在本研究中,我们使用加速衰老的动物模型(SAMP8小鼠)来确定肾组织中维生素C转运体表达的形态学改变和衰老诱导的变化。衰老在SAMP8小鼠的肾脏中引起了显著的形态学变化,如肾小球周围淋巴细胞浸润和肾小球充血,尽管使用双光子显微镜分析和二次谐波产生未观察到胶原沉积增加。最具特征性的组织学改变是近端小管上皮细胞基底外侧区域细胞内空间的扩张。此外,激光显微切割、qRT-PCR和免疫组织化学分析相结合,使我们能够确定在衰老过程中,SVCT1的表达在外髓质外层条带(S3段)和皮质(S2段)的近端小管中特异性增加,并且这些小管也表达GLUT1。我们得出结论,衰老会调节维生素C转运体的表达,并且SVCT1在肾脏中的过表达会增强老年动物(可能合成较少维生素C)对维生素C的重吸收。《细胞生理学杂志》232: 2418 - 2426, 2017。© 2016威利期刊公司