Combined Transcriptomics, Proteomics and Bioinformatics Identify Drug Targets in Spinal Cord Injury.
Combined Transcriptomics, Proteomics and Bioinformatics Identify Drug Targets in Spinal Cord Injury.
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DOI：
10.3390/ijms19051461
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发表时间：
2018-05-14
影响因子：
5.6
通讯作者：
Didangelos A
中科院分区：
文献类型：
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作者：
Tica J;Bradbury EJ;Didangelos A
脊髓损伤(SCI)会造成不可逆转的组织损伤和严重的神经功能丧失。目前，还没有批准的治疗方法，也很少有治疗靶点正在调查中。在这里，我们结合了4个高通量转录组学和蛋白质组学数据集，分别在临床相关的大鼠脊髓损伤后7天和8周识别损伤后持续差异表达的蛋白质。在数以千计的差异调控实体中，我们的联合分析发现，在脊髓损伤后7天和8周，40个显著上调的分子与48个显著下调的分子在mRNA和蛋白质水平上持续变化。然后利用生物信息学分析来确定当前可用的药物对筛选的分子具有活性，并分离在脊髓损伤中具有已知或未知功能的蛋白质。我们的发现揭示了多个被忽视的治疗候选基因，它们具有重要的生物活性和已建立的药理作用，但在脊髓损伤中的表达和功能未知，包括上调的嘌呤核苷磷酸化酶(PNP)、组织蛋白A、H、Z(CTSA、CTSH、CTSZ)和蛋白酶体蛋白酶PSMB10，以及下调的ATP柠檬酸裂解酶(ACLY)、苹果酸酶(ME1)和钠钾ATPase(ATP1A3)等。这项工作揭示了以前未被认可的脊髓损伤治疗候选药物和可用的药物，从而为进一步研究和潜在地重新利用现有的脊髓损伤治疗方法提供了宝贵的资源。
Spinal cord injury (SCI) causes irreversible tissue damage and severe loss of neurological function. Currently, there are no approved treatments and very few therapeutic targets are under investigation. Here, we combined 4 high-throughput transcriptomics and proteomics datasets, 7 days and 8 weeks following clinically-relevant rat SCI to identify proteins with persistent differential expression post-injury. Out of thousands of differentially regulated entities our combined analysis identified 40 significantly upregulated versus 48 significantly downregulated molecules, which were persistently altered at the mRNA and protein level, 7 days and 8 weeks post-SCI. Bioinformatics analysis was then utilized to identify currently available drugs with activity against the filtered molecules and to isolate proteins with known or unknown function in SCI. Our findings revealed multiple overlooked therapeutic candidates with important bioactivity and established druggability but with unknown expression and function in SCI including the upregulated purine nucleoside phosphorylase (PNP), cathepsins A, H, Z (CTSA, CTSH, CTSZ) and proteasome protease PSMB10, as well as the downregulated ATP citrate lyase (ACLY), malic enzyme (ME1) and sodium-potassium ATPase (ATP1A3), amongst others. This work reveals previously unappreciated therapeutic candidates for SCI and available drugs, thus providing a valuable resource for further studies and potential repurposing of existing therapeutics for SCI.
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影响因子：
--
作者：
Chen J;Wang Z;Mao Y;Zheng Z;Chen Y;Khor S;Shi K;He Z;Li J;Gong F;Liu Y;Hu A;Xiao J;Wang X
通讯作者：
Wang X
影响因子：
4.4
作者：
BANIK, NL;HOGAN, EL;SMITH, KP
通讯作者：
SMITH, KP
DOI：
10.1016/s0736-5748(00)00084-8
发表时间：
2001-07-01
影响因子：
1.8
作者：
Ciccarelli, R;Ballerini, P;Di Iorio, P
通讯作者：
Di Iorio, P
影响因子：
5.3
作者：
Geremia, N. M.;Hryciw, T.;Brown, A.
通讯作者：
Brown, A.
影响因子：
4.6
作者：
Abate M;Laezza C;Pisanti S;Torelli G;Seneca V;Catapano G;Montella F;Ranieri R;Notarnicola M;Gazzerro P;Bifulco M;Ciaglia E
通讯作者：
Ciaglia E