Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Department of Anatomy, PTE-MTA PACAP Research Team, University of Pécs Medical School, Pécs, Hungary.
J Alzheimers Dis. 2021;81(3):1195-1209. doi: 10.3233/JAD-201206.
Alzheimer's disease (AD) is a neurodegenerative illness, with several peripheral pathological signs such as accumulation of amyloid-β (Aβ) plaques in the kidney. Alterations of transforming growth factor β (TGFβ) signaling in the kidney can induce fibrosis, thus disturbing the elimination of Aβ.
A protective role of increased physical activity has been proven in AD and in kidney fibrosis, but it is not clear whether TGFβ signalization is involved in this effect.
The effects of long-term training on fibrosis were investigated in the kidneys of mice representing a model of AD (B6C3-Tg(APPswe,PSEN1dE9)85Dbo/J) by comparing wild type and AD organs. Alterations of canonical and non-canonical TGFβ signaling pathways were followed with PCR, western blot, and immunohistochemistry.
Accumulation of collagen type I and interstitial fibrosis were reduced in kidneys of AD mice after long-term training. AD induced the activation of canonical and non-canonical TGFβ pathways in non-trained mice, while expression levels of signal molecules of both TGFβ pathways became normalized in trained AD mice. Decreased amounts of phosphoproteins with molecular weight corresponding to that of tau and the cleaved C-terminal of AβPP were detected upon exercising, along with a significant increase of PP2A catalytic subunit expression.
Our data suggest that physical training has beneficial effects on fibrosis formation in kidneys of AD mice and TGFβ signaling plays a role in this phenomenon.
阿尔茨海默病（AD）是一种神经退行性疾病，在肾脏中有多种外周病理标志，如β淀粉样蛋白（Aβ）斑块的积累。转化生长因子β（TGFβ）信号在肾脏中的改变会诱导纤维化，从而干扰 Aβ的清除。
已经证明增加身体活动对 AD 和肾脏纤维化具有保护作用，但尚不清楚 TGFβ信号是否参与这种作用。
通过比较野生型和 AD 器官，研究了长期训练对 AD 模型小鼠（B6C3-Tg（APPswe，PSEN1dE9）85Dbo/J）肾脏纤维化的影响。用 PCR、western blot 和免疫组织化学法检测经典和非经典 TGFβ信号通路的改变。
长期训练后，AD 小鼠肾脏中胶原 I 型的积累和间质纤维化减少。AD 在未经训练的小鼠中诱导了经典和非经典 TGFβ途径的激活，而在训练的 AD 小鼠中，两种 TGFβ途径的信号分子表达水平恢复正常。在运动过程中，检测到与 tau 和 AβPP 裂解 C 端分子量相对应的磷酸化蛋白的含量减少，同时 PP2A 催化亚基的表达显著增加。
我们的数据表明，体育锻炼对 AD 小鼠肾脏纤维化的形成有有益的影响，TGFβ 信号在这一现象中起作用。
