Renal Function in Aged C57BL/6J Mice Is Impaired by Deposition of Age-Related Apolipoprotein A-II Amyloid Independent of Kidney Aging
Renal Function in Aged C57BL/6J Mice Is Impaired by Deposition of Age-Related Apolipoprotein A-II Amyloid Independent of Kidney Aging
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DOI：
10.1016/j.ajpath.2023.03.002
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发表时间：
2023-06-05
影响因子：
6
通讯作者：
Higuchi，Keiichi
中科院分区：
文献类型：
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作者：
Li，Ying;Dai，Jian;Higuchi，Keiichi
在C57 BL/6 J小鼠中报告了自发性和年龄相关性淀粉样变性。然而，年龄相关性淀粉样变性的生化特征仍不清楚。在此，淀粉样变性的年龄相关的患病率，淀粉样纤维蛋白的类型，和淀粉样蛋白沉积的影响，在C57 BL/6 J小鼠的肾功能进行了研究。获得的结果揭示了来源于杰克逊实验室的C57 BL/6 J小鼠中淀粉样变性的高发病率以及老年小鼠肾小球中大量淀粉样蛋白的沉积。淀粉样纤维蛋白被鉴定为野生型载脂蛋白A-II（ApoA-II）。在40周龄小鼠中诱导淀粉样蛋白沉积，相当于80周龄小鼠的自发发育，以排除衰老的影响，揭示了淀粉样蛋白沉积对肾功能的后续损害。此外，淀粉样蛋白沉积在肾小球系膜区减少足细胞密度，损害足突，并导致肾小球成纤维细胞生长因子2的积累。总的来说，这些结果表明，ApoA-II沉积是老年C57 BL/6 J小鼠的一般病理学，并依赖于供应商的菌落。因此，在对小鼠衰老的研究中需要考虑与年龄相关的淀粉样蛋白沉积的影响。
Spontaneous and age-related amyloidosis has been reported in C57BL/6J mice. However, the biochemical characteristics of age-related amyloidosis remain unclear. Herein, the age-related prevalence of amyloidosis, the types of amyloid fibril proteins, and the effects of amyloid deposition were investigated in renal function in C57BL/6J mice. The results obtained revealed a high incidence of amyloidosis in C57BL/6J mice originating from The Jackson Laboratory as well as the deposition of large amounts of amyloid in the glomeruli of aged mice. The amyloid fibril protein was identified as wild-type apolipoprotein A-II (ApoA-II). Induction of amyloid deposition in 40-week–old mice, equivalent to that of spontaneous development in 80-week–old mice, to rule out the effects of aging, revealed subsequent damage to kidney function by amyloid deposits. Furthermore, amyloid deposition in the mesangial region decreased podocyte density, compromised foot processes, and led to the accumulation of fibroblast growth factor 2 in glomeruli. Collectively, these results suggest that ApoA-II deposition is a general pathology in aged C57BL/6J mice and is dependent on supplier colonies. Therefore, the effects of age-related amyloid deposition need to be considered in research on aging in mice.