Department of Medicine, University Hospital Dubrava, 10 000 Zagreb, Croatia.
Department of Anatomy, Histology and Embryology, University of Split School of Medicine, 21 000 Split, Croatia.
Genes (Basel). 2022 Jun 13;13(6):1053. doi: 10.3390/genes13061053.
Homeostasis of proliferating tissues is strongly dependent on intact DNA. Both neoplastic and non-neoplastic diseases have been associated with MSH2 (MutS homolog 2, a mismatch repair protein) deficiency. In this study, we examined how age and diabetes mellitus influence the expression of MSH2 in the kidney.
To study the effect of age, three groups of healthy rats were formed: 2 months, 8 months, and 14 months old. Two groups of diabetic rats were formed: 8 months old and 14 months old. Expression of MSH2 in the kidney was studied by quantifying immunofluorescent staining.
Age was identified as the main factor that influences MSH2 expression in kidneys. The effect of age followed parabolic dynamics, with peak expression at 8 months of age and similar levels at 2 and 14 months. Diabetes had an age-dependent effect, which manifested as the increase of MSH2 expression in 14-month-old diabetic rats in comparison to healthy animals.
Age influences MSH2 expression in the kidney more than diabetes mellitus. Since ageing is a risk factor for kidney neoplasia, downregulation of MSH2 in older rats might represent one of the pro-oncogenic mechanisms of ageing at a molecular level.
增殖组织的动态平衡强烈依赖于完整的 DNA。肿瘤性和非肿瘤性疾病都与 MSH2(MutS 同源物 2,一种错配修复蛋白)缺陷有关。在这项研究中,我们研究了年龄和糖尿病如何影响肾脏中 MSH2 的表达。
为了研究年龄的影响,将三组健康大鼠分为 2 个月、8 个月和 14 个月龄。将两组糖尿病大鼠分为 8 个月和 14 个月龄。通过定量免疫荧光染色研究 MSH2 在肾脏中的表达。
年龄被确定为影响肾脏中 MSH2 表达的主要因素。年龄的影响呈抛物线动力学,8 个月时表达峰值最高,2 个月和 14 个月时表达水平相似。糖尿病具有年龄依赖性的影响,表现为与健康动物相比,14 个月龄糖尿病大鼠的 MSH2 表达增加。
年龄对肾脏中 MSH2 的表达影响大于糖尿病。由于衰老本身是肾脏肿瘤的一个危险因素,因此在分子水平上,老年大鼠中 MSH2 的下调可能代表衰老的一种致癌机制。