Wang Yixuan, Liu Yonghong, Jin Zhaohui, Liu Cui, Yu Xin, Chen Keke, Meng Detao, Liu Aixian, Fang Boyan
Parkinson Medical Center, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, China.
Beijing Rehabilitation Medical College, Capital Medical University, Beijing, China.
Front Aging Neurosci. 2022 Jun 16;14:909622. doi: 10.3389/fnagi.2022.909622. eCollection 2022.
Rehabilitation has been proposed as a valid measure complementary to the management of Parkinson's disease (PD). However, the mechanism underlying is not clear yet. The differential expressions of exosomal messenger RNA (mRNA) and long noncoding RNAs (lncRNAs) may play a critical role in PD progression and rehabilitation. To compare the differential expressions of exosomal mRNAs and lncRNAs, patients with PD (PWPs, Hoehn and Yahr stages 1.5-2.5, = 6) and age- and sex-matched healthy controls (HCs, = 6) were included in this study. All PWPs received a 2-week rehabilitation treatment in the hospital, which seemingly led to improvement in both the motor and non-motor functions. A set of differentially expressed mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs) extracted from exosomes in blood samples next-generation sequencing (NGS) was screened out. Compared to HCs, 2,337 vs. 701 mRNAs and 1,278 vs. 445 lncRNAs were significantly upregulated and significantly downregulated, respectively, in pre-rehabilitation (pre-rehab) PWPs; 2,490 vs. 629 mRNAs and 1,561 vs. 370 lncRNAs were significantly upregulated and significantly downregulated, respectively, in post-rehabilitation (post-rehab) PWPs. Compared to pre-rehab PWPs, 606 vs. 1,056 mRNAs and 593 vs. 1,136 lncRNAs were significantly upregulated and significantly downregulated, respectively, in post-rehab PWPs. Overall, 14 differentially expressed mRNAs (DEmRNAs) and 73 differentially expressed lncRNAs (DElncRNAs) were expressed in the blood exosomes of HCs, pre- and post-rehab PWPs, simultaneously. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses identified 243 significantly co-expressed lncRNA-mRNA pairs. One DEmRNA of interest (ENSG00000099795, NDUFB7) and three corresponding DElncRNAs (ENST00000564683, ENST00000570408, and ENST00000628340) were positively related. Quantitative real-time polymerase chain reaction (qRT-PCR) validated that the expression levels of NDUFB7 mRNA and the 3 DElncRNAs increased significantly in pre-rehab PWPs, but decreased significantly in post-rehab PWPs compared to HCs. NDUFB7 mRNA is a marker related to mitochondrial respiration. It is reasonably believed that mitochondrial function is associated with PD rehabilitation, and the mitochondrial pathway may involve in the pathogenesis of PD.
康复治疗已被提议作为帕金森病（PD）管理的一种有效补充措施。然而，其潜在机制尚不清楚。外泌体信使核糖核酸（mRNA）和长链非编码核糖核酸（lncRNA）的差异表达可能在PD进展和康复中起关键作用。为了比较外泌体mRNA和lncRNA的差异表达，本研究纳入了PD患者（PWP，Hoehn和Yahr分期1.5 - 2.5，n = 6）以及年龄和性别匹配的健康对照（HC，n = 6）。所有PWP在医院接受了为期2周的康复治疗，这似乎使运动和非运动功能均得到改善。通过下一代测序（NGS）从血液样本的外泌体中筛选出一组差异表达的mRNA（DEmRNA）和差异表达的lncRNA（DElncRNA）。与HC相比，康复前（pre - rehab）PWP中分别有2337个和701个mRNA显著上调和显著下调，1278个和445个lncRNA显著上调和显著下调；康复后（post - rehab）PWP中分别有2490个和629个mRNA显著上调和显著下调，1561个和370个lncRNA显著上调和显著下调。与康复前PWP相比，康复后PWP中分别有606个和1056个mRNA显著上调和显著下调，593个和1136个lncRNA显著上调和显著下调。总体而言，14个差异表达的mRNA（DEmRNA）和73个差异表达的lncRNA（DElncRNA）同时在HC、康复前和康复后PWP的血液外泌体中表达。基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路富集分析确定了243个显著共表达的lncRNA - mRNA对。一个感兴趣的DEmRNA（ENSG00000099795，NDUFB7）和三个相应的DElncRNA（ENST00000564683、ENST00000
