Novel insights into the nervous system affected by prolonged hyperglycemia.
Novel insights into the nervous system affected by prolonged hyperglycemia.
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DOI：
10.1007/s00109-023-02347-y
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发表时间：
2023-08
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--
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包括晚期糖基化终产物受体-透明质酸相关受体1（RAGE-Diaph 1）信号传导在内的多种分子途径在糖尿病周围神经病变（DPN）中发挥作用。有证据表明，1型糖尿病脊髓的神经病理学改变可能发生在周围神经异常的同时或之后。我们证明DPN与周围神经RAGE-Diaph 1信号通路的紊乱相关，伴随着广泛的脊髓分子变化。在糖尿病脊髓中发现了500多个属于多个功能通路的差异表达基因（DEG），其中最丰富的是RAGE-Diaph 1相关的PI 3 K-Akt通路。只有7个脊髓DEG与1型糖尿病坐骨神经DEG重叠，只有一个单一的基因组织蛋白酶E（CTSE）是共同的1型和2型糖尿病小鼠。计算机模拟分析表明，脊髓中的分子变化可能与周围神经中的RAGE-Diaph 1信号轴协同作用。脊髓中的分子扰动可能参与糖尿病周围神经病变的进展。糖尿病周围神经病变与周围神经RAGE-Diaph 1信号通路的紊乱相关，伴有广泛的脊髓分子改变。计算机模拟分析显示，与RAGE-Diaph 1相关的PI 3 K-Akt信号轴是糖尿病脊髓中最丰富的生物学通路。组织蛋白酶E可能是糖尿病周围神经病变干预的靶分子枢纽。在线版本包含补充材料，可通过10.1007/s 00109 -023-02347-y获得。
Multiple molecular pathways including the receptor for advanced glycation end-products-diaphanous related formin 1 (RAGE-Diaph1) signaling are known to play a role in diabetic peripheral neuropathy (DPN). Evidence suggests that neuropathological alterations in type 1 diabetic spinal cord may occur at the same time as or following peripheral nerve abnormalities. We demonstrated that DPN was associated with perturbations of RAGE-Diaph1 signaling pathway in peripheral nerve accompanied by widespread spinal cord molecular changes. More than 500 differentially expressed genes (DEGs) belonging to multiple functional pathways were identified in diabetic spinal cord and of those the most enriched was RAGE-Diaph1 related PI3K-Akt pathway. Only seven of spinal cord DEGs overlapped with DEGs from type 1 diabetic sciatic nerve and only a single gene cathepsin E (CTSE) was common for both type 1 and type 2 diabetic mice. In silico analysis suggests that molecular changes in spinal cord may act synergistically with RAGE-Diaph1 signaling axis in the peripheral nerve. Molecular perturbations in spinal cord may be involved in the progression of diabetic peripheral neuropathy. Diabetic peripheral neuropathy was associated with perturbations of RAGE-Diaph1 signaling pathway in peripheral nerve accompanied by widespread spinal cord molecular changes. In silico analysis revealed that PI3K-Akt signaling axis related to RAGE-Diaph1 was the most enriched biological pathway in diabetic spinal cord. Cathepsin E may be the target molecular hub for intervention against diabetic peripheral neuropathy. The online version contains supplementary material available at 10.1007/s00109-023-02347-y.
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1型和2型糖尿病小鼠坐骨神经的差异基因表达谱
影响因子：
2.3
作者：
Gu Y;Qiu ZL;Liu DZ;Sun GL;Guan YC;Hei ZQ;Li X
通讯作者：
Li X
影响因子：
14.9
作者：
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Tanabe M
影响因子：
7.7
作者：
Juranek JK;Geddis MS;Song F;Zhang J;Garcia J;Rosario R;Yan SF;Brannagan TH;Schmidt AM
通讯作者：
Schmidt AM
影响因子：
3.4
作者：
Juranek, Judyta K.;Geddis, Matthew S.;Schmidt, Ann Marie
通讯作者：
Schmidt, Ann Marie
DOI：
10.3390/life11111267
发表时间：
2021-11-19
期刊：
Life (Basel, Switzerland)
影响因子：
--
作者：
Jaroslawska J;Korytko A;Zglejc-Waszak K;Antonowski T;Pomianowski AS;Wasowicz K;Wojtkiewicz J;Juranek JK
通讯作者：
Juranek JK