Division of Advanced Medical Science, Asahikawa Medical University, Asahikawa 078-8510, Hokkaido, Japan.
Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai 487-8501, Aichi, Japan.
Int J Mol Sci. 2021 Jan 28;22(3):1276. doi: 10.3390/ijms22031276.
Cellular repressor of E1A-stimulated genes 1 (CREG1) is a secreted glycoprotein that accelerates p16-dependent cellular senescence in vitro. We recently reported the ability of CREG1 to stimulate brown adipogenesis using adipocyte P2-CREG1-transgenic (Tg) mice; however, little is known about the effect of CREG1 on aging-associated phenotypes. In this study, we investigated the effects of CREG1 on age-related obesity and renal dysfunction in Tg mice. Increased brown fat formation was detected in aged Tg mice, in which age-associated metabolic phenotypes such as body weight gain and increases in blood glucose were improved compared with those in wild-type (WT) mice. Blood CREG1 levels increased significantly in WT mice with age, whereas the age-related increase was suppressed, and its levels were reduced, in the livers and kidneys of Tg mice relative to those in WT mice at 25 months. Intriguingly, the mRNA levels of , , and senescence-associated secretory phenotype (SASP)-related genes and p38MAPK activity were significantly lowered in the aged kidneys of Tg mice, in which the morphological abnormalities of glomeruli as well as filtering function seen in WT kidneys were alleviated. These results suggest the involvement of CREG1 in kidney aging and its potential as a target for improving age-related renal dysfunction.
细胞 E1A 刺激基因 1 （CREG1）的抑制剂是一种分泌型糖蛋白，它可以在体外加速 p16 依赖性细胞衰老。我们最近报道了 CREG1 能够使用脂肪细胞 P2-CREG1 转基因（Tg）小鼠刺激棕色脂肪生成的能力；然而，对于 CREG1 对衰老相关表型的影响知之甚少。在这项研究中，我们研究了 CREG1 对 Tg 小鼠与年龄相关的肥胖和肾功能障碍的影响。在年老的 Tg 小鼠中检测到棕色脂肪形成增加，与野生型（WT）小鼠相比，体重增加和血糖升高等与年龄相关的代谢表型得到改善。WT 小鼠随年龄增长血 CREG1 水平显著升高，而 Tg 小鼠则抑制了与年龄相关的 CREG1 增加，其肝脏和肾脏中的 CREG1 水平相对于 WT 小鼠在 25 个月时降低。有趣的是，Tg 小鼠年老肾脏中 、 和衰老相关分泌表型（SASP）相关基因的 mRNA 水平以及 p38MAPK 活性显著降低，WT 肾脏中肾小球的形态异常以及过滤功能得到缓解。这些结果表明 CREG1 参与了肾脏衰老及其作为改善与年龄相关的肾功能障碍的靶标的潜力。
