canonical pathways ipa

J. Neurobiol. Poor growth of Mammalian motor and sensory axons into intact proximal nerve stumps. Similar as the results from canonical pathway analysis, diseases and functions with a p-value less than 10−5 as well as involved representative genes are listed in Figure 3. Supplementary Table 2. Differential gene expression profiling and biological process analysis in proximal nerve segments after sciatic nerve transection. At 6 to 24 h post injury, diseases and cellular functions related to organ development, tissue and organ morphology, tissue disorder, as well as organismal survival and function were significantly activated. However, the up-regulation of MMP9 was largely compromised in mice with delayed Wallerian degeneration (Shubayev et al., 2006; Barrette et al., 2010). doi: 10.1006/exnr.1995.1039, PubMed Abstract | CrossRef Full Text | Google Scholar, Barrette, B., Calvo, E., Valliéres, N., and Lacroix, S. (2010). Figure 2. All animal procedures were ethically approved by the Administration Committee of Experimental Animals, Jiangsu Province, China and were used in accordance with Institutional Animal Care guideline of Nantong University. A p-value less than 0.05 was considered as significantly different. RNA for sequencing was extracted from epithelial cells at 48 h post-infection with 5 strains at a multiplicity of infection of approximately 10:1. Orthop. 29, 321–332. Degeneration of myelinated efferent fibers prompts mitosis in Remak Schwann cells of uninjured C-fiber afferents. Top canonical pathways mapped in IPA (A) and GO terms (B) classified under biological process.In (A) the bar chart on the left represents the percentage of gene Neural Regen. Scordo JM, Olmo-Fontánez AM, Kelley HV, Sidiki S, Arcos J, Akhter A, Wewers MD, Torrelles JB. The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. Hierarchical clustering for enrichment of cholesterol biosynthesis and immune associated pathways revealed similar patterns for Beijing and Unique; F15/LAM4/KZN and F11; and, F28 and H37Rv strains, respectively. doi: 10.1016/j.mcn.2005.10.011, Sta, M., Cappaert, N. L., Ramekers, D., Baas, F., and Wadman, W. J. Lett. Prevention and treatment information (HHS). Neurosci. To further validate the gene expression profiles identified by microarray analysis, some representative differentially expressed genes involved in Nervous System Development and Function were selected for qRT-PCR examination (Figure 6). 49, 233–243. Infection and RNA-seq analysis of a zebrafish tlr2 mutant shows a broad function of this toll-like receptor in transcriptional and metabolic control and defense to Mycobacterium marinum infection. doi: 10.1097/WCO.0b013e32834c208d, Bosse, F., Hasenpusch-Theil, K., Kury, P., and Müller, H. W. (2006). Neurol. Schwann cell properties: 3. QIAGEN Ingenuity Pathway Analysis helps you perform insightful data analysis and interpretation to understand your experimental results … Gene expression profiling of the rat sciatic nerve in early Wallerian degeneration after injury. 27 The Upstream Analysis feature of IPA was used to predict the activation or inhibition of transcriptional regulators based on the direction of gene expression changes in our data set. Conceived and designed the experiments: JY, XG and SY. 15:25-22:35 Core Analysis Canonical Pathway results. Exp. Wrote the manuscript: SY. Rev. Autophagic myelin destruction by Schwann cells during Wallerian degeneration and segmental demyelination. At 0.5 h post sciatic nerve transection, only Interleukin-17A (IL-17A) Signaling in Airway Cells (an IL-17 cytokine signaling) and TREM1 Signaling (a proinflammatory immune response) are significantly activated. IPA, Ingenuity pathway analysis; SD, Sprague-Dawley; IPKB, Ingenuity pathway knowledge base; qPCR, quantitative real time polymerase chain reaction; IL, Interleukin; MMP, matrix metalloproteinase; BDNF, brain derived neurotrophic factor; SHH, sonic hedgehog; MAG, myelin-associated glycoprotein; MAL, myelin and lymphocyte protein; SLC6A17, solute carrier family 6 member 17; ECM, extracellular matrix. doi: 10.1111/j.1460-9568.1991.tb00069.x, Brown, M. C., Lunn, E. R., and Perry, V. H. (1992). FOIA The rats in the 0 h group received sham-surgery on their left sciatic nerves were used as controls. Table 2. (2013). Differentially expressed genes involved in Nervous System Development and Function at 0.5, 1, 6, 12, and 24 h, 4 days, and 1, 2, and 3 weeks post sciatic nerve transection. Microarray analysis was performed by an Affymetrix GeneChip Hybridization Oven 640 and Gene Array Scanner 3000. Bioinformatics analysis performed with the RNA-Seq Tuxedo pipeline identified differentially expressed genes. COVID-19 is an emerging, rapidly evolving situation. 36:51-37:19 My Lists, My Pathways, and Molecules tab Int. Curr. Mol Microbiol. Epub 2014 Oct 18. It may be because that at an early stage after nerve injury only non-myelinating Schwann cells, but not myelinating Schwann cells, enter into the cell cycle to avoid negative factors for nerve regeneration (Murinson et al., 2005), but later on myelinating Schwann cells start to proliferate and to form myelin sheaths (Liu et al., 1995; Vargas and Barres, 2007). Neurosci. Neurol. Figure 5. J. Neurosci. J. Neurol. Nihon Saikingaku Zasshi. Signal flow and pathways in response to early Wallerian degeneration after rat sciatic nerve injury. 10:274. doi: 10.3389/fncel.2016.00274. (2014). The examination for the genes involved in Nervous System Development and Function indicated that MMP9 and BDNF were significantly up-regulated starting from 6 h post nerve injury. Res. Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury. Our earlier studies also demonstrated that two other members of the MMP family, MMP7 and MMP12, were kept up-regulated following nerve injury (Jiang et al., 2014; Qin et al., 2016). 193, 334–340. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. An Overview of the Canonical Pathways in IPA Causal Networks Ingenuity Pathway Analysis (IPA) | Advanced Analytics - Generate virtual upstream regulators which are networks of regulators Upstream Regulators Analysis Tutorial Ingenuity Pathway Analysis (IPA) Small RNA Mcr11 requires the transcription factor AbmR for stable expression and regulates genes involved in the central metabolism of Mycobacterium tuberculosis. The differentially expressed genes involved in Nervous System Development and Function are listed in Supplementary Table 5. Am. doi: 10.1093/nar/gkv007, Shubayev, V. I., Angert, M., Dolkas, J., Campana, W. M., Palenscar, K., and Myers, R. R. (2006). (2016). The significance of the association between the dataset and a canonical pathway was determined doi: 10.1007/s00401-015-1482-4, Chen, Z. L., Yu, W. M., and Strickland, S. (2007). BDNF is a well-known neurotrophic factor that promotes neuronal survival and activity and stimulates axon growth (Braun et al., 1996; Lykissas et al., 2007). Pathway/Tox List 搜尋 IPA內建有 Ingenuity Canonical Pathways 與 Toxicity Lists Library資料。例如可以找到Hepatic Cholestasis相關的毒物以及Signaling Pathway資料。此搜尋是針對該內建資料庫，您需要輸入 pathway的名稱作為關鍵字搜尋。 IV. Notably, a cellular function highly related to nerve regeneration, which is called Nervous System Development and Function, was continuously activated from 4 days until 4 weeks post injury. All categories of diseases and functions and their associated genes are listed in Supplementary Table 3. Briefly, rats were anesthetized by an injection of mixed narcotics (85 mg/kg trichloroacetaldehyde monohydrate, 42 mg/kg magnesium sulfate, and 17 mg/kg sodium pentobarbital). We have previously reported on the up-regulation of the mRNA expression of BDNF at 1, 4, 7, and 14 days post nerve crush injury (Yi et al., 2016). Schwann cells, neurotrophic factors, and peripheral nerve regeneration. Ingenuity® Pathway Analysis (IPA) software was used to conduct pathway enrichment based on the recruited gene datasets mentioned above. doi: 10.4103/1673-5374.135325, Kim, Y., Remacle, A. G., Chernov, A. V., Liu, H., Shubayev, I., Lai, C., et al. J Med Microbiol. Annu. 30, 153–179. Gene networks and their related top diseases and functions are listed in Supplementary Table 4. Build custom pathways and gene or chemical list libraries Create custom pathways with My Pathways and gene or chemical list libraries from a range of input data: gene lists from IPA search results, existing IPA networks or canonical pathways, uploaded lists of targets or biomarkers, or imported pathways using XGMML, BioPax, SBML, or GPML. In the Canonical Pathways function of IPA, pathways were considered to be significantly dysregulated if they were associated with a right-tailed Fisher's exact p-value < 0.01. J. Neurosci. Different from the central nervous syst… Figure 4. 79, 198–208. In this study, we applied microarray to identify differentially expressed genes in the distal nerve stumps after sciatic nerve transection, and further used IPA program as the main bioinformatic tool to analyze microarray data. Biological processes, such as response to stimulus, inflammatory response, immune response, cell proliferation, migration, and apoptosis, axon guidance, myelination, signal transduction, and protein kinase activity, were also investigated (Jiang et al., 2014). The microenvironment of injured and regenerating peripheral nerves. This session focus on formatting your own data and the best practices to analyze them in IPA. 9, 1186–1194. Curr. IPA was performed to identify canonical pathways, diseases and functions, and gene networks that are most significant to microarray outcomes and to categorize differentially expressed genes in specific diseases and functions. Methods 222, 189–198. 125, 2675–2683. List of all categories of canonical pathways and involved molecules following sciatic nerve transection. Microarray analysis showed that a few genes were differentially expressed at 0.5 and 1 h post nerve injury and later on a relatively larger number of genes were up-regulated or down-regulated. Figure 1. 2016 Dec;65:321-329. doi: 10.1016/j.dci.2016.07.022. Adult male Sprague-Dawley (SD) rats, body weight 180–200 g, were purchased from the Experimental Animal Center of Nantong University and housed in temperature- and humidity-controlled large cages with sawdust bedding and given access to tap water and food ad libitum. Starting from 6 h post injury, a larger number of canonical pathways were activated, which were mainly related to inflammation and immune response, cytokine signaling, diseases, nuclear receptor signaling, and intracellular and second messenger signaling. BMC Genomics. Careers. Opin. 6, 391–407. Supplementary Table 1. Front. At 0.5, 1, 6, 12, and 24 h post nerve injury, top networks had scores of 21, 23, 23, 27, and 29, respectively. doi: 10.1016/0022-510X(95)00315-S, Brown, M. C., Lunn, E. R., and Perry, V. H. (1991). Eur. Fortunately, the progress in bioinformatic analysis allows us to better interpret the gene expression profiles as revealed by microarray. The heapmap suggested that nearly 2/3 of genes involved in this cellular function were firstly up-regulated and then down-regulated while a little bit less than 1/3 of differentially genes were first down-regulated and then up-regulated. The QIAGEN Ingenuity Pathway Analysis (IPA) is intended for molecular biology applications. Int. IPA will subdivide your data into slices based on molecule connectivity (networks), cellular functions, and involvement in canonical pathways Spend time surveying the information. The MMP-9/TIMP-1 axis controls the status of differentiation and function of myelin-forming Schwann cells in nerve regeneration. limma powers differential expression analyses for RNA-sequencing and microarray studies. Neurobiol. Expert Rev Proteomics. Sci. 87, 27–46. Rep. 6:29121. doi: 10.1038/srep29121, Yi, S., Zhang, H., Gong, L., Wu, J., Zha, G., Zhou, S., et al. Analyzed the data: JY and SY. Chapter 3: histology of the peripheral nerve and changes occurring during nerve regeneration. 96, 1441–1457. Acad. doi: 10.1523/JNEUROSCI.1372-04.2005, Qin, J., Zha, G. B., Yu, J., Zhang, H. H., and Yi, S. (2016). Our results may help to illuminate the molecular aspects of Wallerian degeneration and to develop potential therapeutic targets for peripheral nerve repair. This product is not intended for the diagnosis, prevention, or treatment of a disease. Macrophage recruitment in different models of nerve injury: lysozyme as a marker for active phagocytosis. |, https://www.frontiersin.org/article/10.3389/fncel.2016.00274/full#supplementary-material, Creative Commons Attribution License (CC BY), Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China. Hadifar S, Mostafaei S, Behrouzi A, Fateh A, Riahi P, Siadat SD, Vaziri F. BMC Bioinformatics. To further identify key genes involved in this cellular function and establish the connections in-between these genes, the gene network diagrams were made based on IPKB. 536, 56–63. doi: 10.1002/mus.24082, Li, S., Liu, Q., Wang, Y., Gu, Y., Liu, D., Wang, C., et al. Schwann cells and endoneurial extracellular matrix molecules as potential cues for sorting of regenerated axons: a review. Privacy, Help doi: 10.3892/ijmm.6.4.391, Ritchie, M. E., Phipson, B., Wu, D., Hu, Y., Law, C. W., Shi, W., et al. Data are summarized from 3 independent experiments and values are shown as the means ± SEM. Rev. Canonical Pathways：IPA科学家们手工绘制了800多种生物信号通路和代谢通路，在Canonical Pathways分析对与实验数据最相关的失调通路进行打分，查看背景知识和支持文献，查询通路分子互作实验信息，利用Build，Overlay和Path Designer工具对通路进行个性化编辑与扩展。 J. Neurosci. Consistent with the results of canonical pathway analysis, following sciatic nerve transection, the number of categories of diseases and functions first increased and then progressively declined. (2013). 54, 487–496. ＊PMCでIngenuity Pathway Analysisを検索をした結果 ナレッジ＆データベース 遺伝子、タンパク質、組織、細胞、ドラッグ、疾患などに関する、約760万（2020年10月現在）にもおよぶ生物学的機能、相互作用に関する情報が収集されたデータベースです。 9, S33–S38. Lett. Unable to load your collection due to an error, Unable to load your delegates due to an error. Epub 2016 Aug 3. Nerves are fragile tissues that are susceptible to traumatic injuries, such as penetration, crushing, and stretch tractions (Campbell, 2008). Neurovasc. Differential gene expression in proximal and distal nerve segments of rats with sciatic nerve injury during Wallerian degeneration. Clin. The IPA system (version 42012434, Ingenuity Systems; Qiagen China Co., Ltd.) was used for subsequent bioinformatics analysis, which included canonical pathway analysis, disease and function, regulator effects, upstream regulators and molecular networks. Neurol. J. Neurosci. Changes in pathways, networks and transcriptional factors were identified using Ingenuity Pathway Analysis (IPA). 2021 Mar 25;22(1):154. doi: 10.1186/s12859-021-04100-z. Neurosci. f4-ijmm-35-06-1511: Ingenuity Pathway Analysis (IPA) canonical pathways most significantly changed in third-trimester peripheral blood NK (pNK) cells compared to first-trimester pNK cells. PLoS ONE 8:e57000. Regulation of Schwann cell proliferation and migration by miR-1 targeting brain-derived neurotrophic factor after peripheral nerve injury. Wallerian degeneration: gaining perspective on inflammatory events after peripheral nerve injury. An integrated global view of gene expression patterns during Wallerian degeneration was obtained by performing IPA core analysis, overlaying microarray data to IPKB, and then assigning differentially expressed genes to specific canonical pathways, diseases and biological functions, and networks. Muscle Nerve Suppl. The authors thank Professor Jie Liu for his help in manuscript preparation. Canonical pathways with a p-value < 10−3 (1E-03) are labeled in red color while canonical pathways with a p-value > 10−3 (1E-03) are labeled in white color. Consequences of slow Wallerian degeneration for regenerating motor and sensory axons. At 0.5, 1, 6, 12, and 24 h, 4 days, and 1, 2, 3, and 4 weeks after surgery, rats were sacrificed by decapitation. Supplementary Figure 1. Up-regulated MMP9 stimulates the recruitment and migration of macrophages, mediates the differentiation of myelinating Schwann cells, and thus benefits nerve regeneration (Shubayev et al., 2006; Kim et al., 2012). With QIAGEN IPA you can predict downstream effects and identify new targets or candidate biomarkers. Different from the central nervous system that can hardly regenerate by itself, the peripheral nervous system has a certain ability to regenerate on its own (Raimondo et al., 2011; Gu et al., 2014). Supplementary Table 3. Wallerian degeneration and peripheral nerve conditions for both axonal regeneration and neuropathic pain induction. Wallerian degeneration in the distal nerve stump contributes to the construction of a permissible microenvironment for peripheral nerve regeneration. List of differentially expressed genes involved in Nervous System Development and Function following sciatic nerve transection. Res. The sequences of primer pairs were listed in Supplementary Table 1. We analyzed the global differential gene expression of a GBM cell line HTB15 in comparison to normal human Astrocytes, and established a few canonical pathways that are important in determining the molecular mechanisms of cancer using global gene expression microarray, coupled with the Ingenuity Pathway Analysis (IPA®). doi: 10.2174/156720207780637216, Murinson, B. 2010 May;59(Pt 5):528-533. doi: 10.1099/jmm.0.016006-0. Canonical Pathway Z-scores – Allows you to quickly determine if Canonical Pathways, including functional end-points, are increased or decreased based on differentially expressed genes or proteins in your data set – Certain pathways within the knowledge base are directional (proceed from “A” to “Z”) Not everything is of scientific interest, look for slices of your data that address your scientific question, are consistent 209, 378–388. (2016). Surg. J. Neuroinflammation 8:110. doi: 10.1186/1742-2094-8-110, Geuna, S., Raimondo, S., Ronchi, G., Di Scipio, F., Tos, P., Czaja, K., et al. In this study, besides MMP9 and BDNF, myelin-related genes (MAG and MAL) were also found to be up-regulated starting from 4 days post injury. Performed the experiments: JY and SY. At 1 h post injury, significant activated cellular functions were generally related to inflammation and immune response, tissue development, and numerous diseases. Detected global gene expressions at each time point following sciatic nerves transection were compared with the control group. Sonic hedgehog (SHH) was first up-regulated at 6 h post injury and then down-regulated at later time points. Res. The functional and morphological characteristics of sciatic nerve degeneration and regeneration after crush injury in rats. Biomaterials 35, 6143–6156. doi: 10.1016/j.bbi.2010.07.249, Benowitz, L. I., and Popovich, P. G. (2011). doi: 10.1146/annurev.neuro.30.051606.094337, David, S., Braun, P. E., Jackson, D. L., Kottis, V., and McKerracher, L. (1995). doi: 10.5435/00124635-200007000-00005, Li, M., Guo, W., Zhang, P., Li, H., Gu, X., and Yao, D. (2013). doi: 10.1371/journal.pone.0033664, Lee, S. K., and Wolfe, S. W. (2000). doi: 10.1016/j.neulet.2013.01.008, Li, M., Zhang, P., Guo, W., Li, H., Gu, X., and Yao, D. (2014). doi: 10.1371/journal.pone.0057000, Liu, H. M., Yang, L. H., and Yang, Y. J. Hu W, Yang S, Shimada Y, Münch M, Marín-Juez R, Meijer AH, Spaink HP. Among these gene network diagrams, a diagram related to 4 weeks post nerve injury is shown in Figure 5, and other diagrams related to other time points are shown in Supplementary Figure 1. Int. Timely inflammatory and immune reactions are highly relevant with Wallerian degeneration, and benefit subsequent nerve repair and functional recovery (Dubový, 2011; Gaudet et al., 2011). As indicated by all diagrams, IL-6 was immediately up-regulated at 0.5 h post nerve injury and highly expressed at all tested time points; with the passage of time, more genes were differentially expressed and the molecular network seemed more complex. 2019 May;12(3):795-804. doi: 10.1038/s41385-019-0156-2. 8, 243–252. J. Mol. The Wallerian degeneration process, since its first observation by Augustus Volney Waller in 1850, has been widely studied. The expression levels of genes were indicated by the color bar above the heatmap. Limited knowledge exists on pathways, networks and transcriptional factors regulated within epithelial cells by diverse Mycobacterium tuberculosis genotypes. Role of macrophages in Wallerian degeneration and axonal regeneration after peripheral nerve injury. 11, 1165–1171. During tissue remodeling, MMPs mediate the breakdown of the extracellular matrix (ECM), a key network containing physical and biochemical cues for tissue regeneration (Ravanti and Kähäri, 2000; Dubový, 2004; Chen et al., 2007). Med. Certainly, the gene expression patterns and activated biological processes in the distal nerve stump showed different characteristics compared to those in the proximal nerve stump. Total RNA was extracted with Trizol reagent (Life technologies, Carlsbed, CA) and cleaned with RNeasy spin columns (Qiagen, Valencia, CA). The interferon signalling and hepatic fibrosis/hepatic stellate cell activation pathways were among the top 5 canonical pathways in all strains. PLoS ONE 10:e0143491. Keywords: J. Mol. Mvubu NE, Pillay B, McKinnon LR, Pillay M. Cytokine. There has been a previous study which compared the differentially gene expressions in proximal and distal nerves after nerve injury (Jiang et al., 2014). 30, 209–233. Cell. These top networks are generally associated with cellular morphology, assembly, organization, and organ development. 2019 Nov 20;20(1):878. doi: 10.1186/s12864-019-6265-1. The involvement of Nervous System Development and Function at different time points. Obtained cDNA was used as a template for amplification and qPCR was performed using SYBR Green Premix Ex Taq (TaKaRa) with specific primer pairs on an Applied Biosystems Stepone real-time PCR System. Among the transcriptional factors, only EHL, IRF7, PML, STAT1, STAT2 and VDR were induced by all clinical strains. Immediately after peripheral nerve injury, the most significant pathways and cellular functions were found to be inflammatory and immune response, which remained to be activated until 4 weeks post nerve injury. Anat. (2012). It should be known that the proximal and the distal nerve stumps may share many common genes but have different spatiotemporal expression patterns after nerve injury. Myelin is an important inhibiting factor for neurite growth and nerve repair (Bähr and Przyrembel, 1995; David et al., 1995). Neurophysiol. (2012). IPA provides two powerful tools to understand the pathway analysis results: the networks and canonical pathways that showed several pathways related to an adaptative immune response. At relatively later time points post peripheral nerve injury, the most significant canonical pathways and cellular functions were found to be tissue development and function. Gene expression profiling reveals that peripheral nerve regeneration is a consequence of both novel injury-dependent and reactivated developmental processes. Ingenuity Pathway Analysis (IPA) was used to investigate canonical pathways and immunohistochemical staining was performed to validate protein expression levels in samples. Accessibility Received: 12 September 2016; Accepted: 15 November 2016; Published: 06 December 2016. qPCR outcomes were expressed as means ± SEM, and analyzed by means of SPSS 15.0 software (SPSS, Chicago, IL). (2015). The role of neurotrophins in axonal growth, guidance, and regeneration. 23, 521–536. All these results highlight the central roles of the MMP family in nerve regeneration.

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