Cell Sci. Nucleic Acids Res. Supplementary Figure 1. This study was supported by the Natural Science Foundation of Jiangsu Province, China (Grant No. 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. Morphological observation of Wallerian degeneration suggests that macrophages migrate to the injured site in an early stage post injury (Geuna et al., 2009). The Supplementary Material for this article can be found online at: https://www.frontiersin.org/article/10.3389/fncel.2016.00274/full#supplementary-material. 6, 391–407. The thermal setting was 5 min at 95°C; 40 cycles of 30 seconds at 95°C, 45 seconds at the annealing temperature, 30 seconds at 72°C; and 5 min at 72°C. Different from the central nervous system, the peripheral nervous system is able to regenerate after injury. All authors have read and approved the final manuscript. Baclofen modulates the expression and release of neurotrophins in schwann-like adipose stem cells. 15:25-22:35 Core Analysis Canonical Pathway results. Consequences of slow Wallerian degeneration for regenerating motor and sensory axons. J. Neurosci. These top networks were mainly connected to the functions: Cellular Movement and Cell-To-Cell Signaling. Moreover, our finding that inflammation and immune response was continuously activated is consistent with previous observation in a model of sciatic nerve crush injury (Yi et al., 2015). At 1 h post injury, significant activated cellular functions were generally related to inflammation and immune response, tissue development, and numerous diseases. J. Neurol. Neurosci. Bethesda, MD 20894, Copyright Top enriched networks following sciatic nerve transection. Further in-depth studies are needed to determine which genes and functions represent the key molecular elements for peripheral nerve regeneration. Schwann cells and endoneurial extracellular matrix molecules as potential cues for sorting of regenerated axons: a review. Ann. Epub 2010 Jan 28. Neurosci. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). Received: 12 September 2016; Accepted: 15 November 2016; Published: 06 December 2016. Glia 64, 730–742. Neurophysiol. Anat. 3, 1366–1369. Matrix metalloproteinases in wound repair (review). 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. doi: 10.5435/00124635-200007000-00005, Li, M., Guo, W., Zhang, P., Li, H., Gu, X., and Yao, D. (2013). Role of macrophages in Wallerian degeneration and axonal regeneration after peripheral nerve injury. These top networks are generally associated with cellular morphology, assembly, organization, and organ development. Exp. Muscle Nerve Suppl. 10:274. doi: 10.3389/fncel.2016.00274. 23, 521–536. doi: 10.2174/156720207780637216, Murinson, B. Limited knowledge exists on pathways, networks and transcriptional factors regulated within epithelial cells by diverse Mycobacterium tuberculosis genotypes. Ingenuity Pathways Analysis (IPA) IPA is a web-based bioinformatics application that allows researchers to upload data analysis results from high-throughput experiments such as microarray and next generation sequencing for functional analyze, integration, and further understanding. Nerves are fragile tissues that are susceptible to traumatic injuries, such as penetration, crushing, and stretch tractions (Campbell, 2008). 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. Acad. Previous studies also revealed that the MMP9 expression was often elevated following 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. With the development of high-throughput genomic tools, such as microarray analysis and deep sequencing, it is now possible and preferable to detect the gene expression changes during Wallerian degeneration in order to identify the molecular basis of the morphological changes. 9, S33–S38. A p-value less than 0.05 was considered as significantly different. Wrote the manuscript: SY. doi: 10.3892/ol.2015.3472, Yao, D., Li, M., Shen, D., Ding, F., Lu, S., Zhao, Q., et al. eCollection 2021. Copyright © 2015 Elsevier Ltd. All rights reserved. The gene list was loaded, and the source of the organism was filtered as only “Homo Sapiens”, so that the analysis of interactions and pathways was limited to humans. Analyzed the data: JY and SY. doi: 10.3969/j.issn.1673-5374.2012.17.001, Yao, D., Li, M., Shen, D., Ding, F., Lu, S., Zhao, Q., et al. Stored distal nerve stumps were used for total RNA isolation. 2020 Feb;113(2):504-520. doi: 10.1111/mmi.14436. doi: 10.4103/1673-5374.187059, Raimondo, S., Fornaro, M., Tos, P., Battiston, B., Giacobini-Robecchi, M. G., and Geuna, S. (2011). J. Mol. 25, 1179–1187. Neurol. IPA results provided us with some new insights into Wallerian degeneration. This product is not intended for the diagnosis, prevention, or treatment of a disease. The expression levels of genes were indicated by the color bar above the heatmap. Ingenuity pathway analysis indicated that inflammation and immune response, cytokine signaling, cellular growth and movement, as well as tissue development and function were significantly activated following sciatic nerve injury. This session focus on formatting your own data and the best practices to analyze them in IPA. 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). Neurol. 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. Eur. J. Neuropathol. Res. Bull. It has been known that after peripheral nerve injury, Schwann cells not only proliferate to form the bands of Bungner, but also produce a range of neurotrophic factors, including BDNF (Frostick et al., 1998; Faroni et al., 2013; Jang et al., 2016). Macrophage recruitment in different models of nerve injury: lysozyme as a marker for active phagocytosis. Bähr, M., and Przyrembel, C. (1995). Front. Res. To investigate peripheral nerve injury-induced molecular changes during Wallerian degeneration, microarray analysis was performed to detect the expression levels of more than 30,000 genes at 0, 0.5, 1, 6, 12, and 24 h, 4 days, and 1, 2, 3, and 4 weeks in the distal nerve stumps post sciatic nerve transection. 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) doi: 10.1093/nar/gkv007, Shubayev, V. I., Angert, M., Dolkas, J., Campana, W. M., Palenscar, K., and Myers, R. R. (2006). 9, 1186–1194. The stacked bar chart displays the percentage of genes that were upregulated (red), downregulated (green), and genes not overlapping with our data set (white) in each canonical pathway. 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. Small RNA Mcr11 requires the transcription factor AbmR for stable expression and regulates genes involved in the central metabolism of Mycobacterium tuberculosis. Immun. Microarray analysis was performed by an Affymetrix GeneChip Hybridization Oven 640 and Gene Array Scanner 3000. 4, 143–151. Furthermore, many statistical and bioinformatic tools, including Hierarchical clustering, Euclidean distance matrix, Venny plot analysis, Volcano plot analysis, principal component analysis, Gene Ontology analysis, and Kyoto Enrichment of Genes and Genomes pathway analysis, have been applied to determine key molecules, signaling pathways, and biological processes during Wallerian degeneration. 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. All these results highlight the central roles of the MMP family in nerve regeneration. doi: 10.1016/j.bbi.2010.07.249, Benowitz, L. I., and Popovich, P. G. (2011). It is worth noting that cellular function Nervous System Development and Function was vastly involved in many gene networks at nearly all tested time points, except at 0.5 and 1 h post injury (Table 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. B., Archer, D. R., Li, Y., and Griffin, J. W. (2005). 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. Top enriched diseases and functions following sciatic nerve transection. Res. Res. (2007). 23:32-28:27 Upstream Analysis results. Annu. *Correspondence: Sheng Yi, syi@ntu.edu.cn, Front. In addition to canonical pathways, differentially expressed genes were also categorized to related diseases and functions. All categories of diseases and functions and their associated genes are listed in Supplementary Table 3. Ann. Differential temporal expression of matrix metalloproteinases following sciatic nerve crush. Epub 2014 Oct 18. National Library of Medicine doi: 10.1002/glia.22957, Jiang, N., Li, H., Sun, Y., Yin, D., Zhao, Q., Cui, S., et al. Differential gene expression profiling and biological process analysis in proximal nerve segments after sciatic nerve transection. Nerve injury disturbs signal transmission, causes loss or alteration of sensation, impairs the power and function of target organs, and leads to disability and even mortality of victims. doi: 10.1016/j.aanat.2011.02.011, Dubový, P., Jancalek, R., and Kubek, T. (2013). doi: 10.1016/j.expneurol.2007.06.009, Dubový, P. (2004). Evaluation and management of peripheral nerve injury. 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: 10.1371/journal.pone.0033664, Lee, S. K., and Wolfe, S. W. (2000). The sequences of primer pairs were listed in Supplementary Table 1. Neurol. Figure 3. (2015). Methods 222, 189–198. Rat sciatic nerve was exposed through an incision on the lateral aspect of the mid-thigh of the left hind limb and a 10-mm nerve segment was excised.
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