Transcriptomic responses to wounding: meta-analysis of gene expression microarray data

Abstract

BackgroundA vast amount of microarray data on transcriptomic response to injury has been collected so far. We designed the analysis in order to identify the genes displaying significant changes in expression after wounding in different organisms and tissues. This meta-analysis is the first study to compare gene expression profiles in response to wounding in as different tissues as heart, liver, skin, bones, and spinal cord, and species, including rat, mouse and human.ResultsWe collected available microarray transcriptomic profiles obtained from different tissue injury experiments and selected the genes showing a minimum twofold change in expression in response to wounding in prevailing number of experiments for each of five wound healing stages we distinguished: haemostasis & early inflammation, inflammation, early repair, late repair and remodelling. During the initial phases after wounding, haemostasis & early inflammation and inflammation, the transcriptomic responses showed little consistency between different tissues and experiments. For the later phases, wound repair and remodelling, we identified a number of genes displaying similar transcriptional responses in all examined tissues. As revealed by ontological analyses, activation of certain pathways was rather specific for selected phases of wound healing, such as e.g. responses to vitamin D pronounced during inflammation. Conversely, we observed induction of genes encoding inflammatory agents and extracellular matrix proteins in all wound healing phases. Further, we selected several genes differentially upregulated throughout different stages of wound response, including established factors of wound healing in addition to those previously unreported in this context such as PTPRC and AQP4.ConclusionsWe found that transcriptomic responses to wounding showed similar traits in a diverse selection of tissues including skin, muscles, internal organs and nervous system. Notably, we distinguished transcriptional induction of inflammatory genes not only in the initial response to wounding, but also later, during wound repair and tissue remodelling.Electronic supplementary materialThe online version of this article (10.1186/s12864-017-4202-8) contains supplementary material, which is available to authorized users.

Appendage regeneration in anamniotes utilizes genes active during larval‐metamorphic stages that have been lost or altered in amniotes: The case for studying lizard tail regeneration

“…The examination of genes resulting from transcriptomes of mammalian healing skin, liver or other organs (Li et al, 2001; Khaspur et al, 2013; Sass et al, 2017; Rib et al, 2018), also evidences differences with those of anamniotes, particularly the expression of numerous genes involved in inflammation and immunity (Table 3). In the regenerating lizard tail (Hutchins et al, 2014), but not in the scarring limb (Vitulo et al, 2017a), several oncogenes (e.g., wnt2b , wnt5a , wnt 5b , wnt1 , wnt10 , fgf8 , fgfr4 , snoRNAs) and some tumor‐suppressors (e.g., apc , arhgap28 , fat2 , rb ) are activated (Tables 3 and 4).…”

“…Amphibian (newt), Elewa et al (2017) Mouse (organs healing), Sass et al (2017) dnmt, twist1, rbp2a, mmp11, tbx5, roa1, hnrnp1, hnrnp2, hnrnp3, sfrs1, cirbp, ptma, sfrs1, fus, hnRNPa1, hoxa13, krt17, tecta, crdl1, emx2, apcdd1, cd38, shox anxa1, anxa2, ccl2, cd44, icam1, Igals3, mmp12, ptprc, spp1, timpl, aqp4…”

“…The contemporaneous presence of genes for adaptive immunity, complex nervous circuits, or for other amniote functions somehow determines regeneration failure, as schematically indicated in Figure 5b,c. The analysis of the transcriptomes of healing skin and other mammalian organs (Brant et al, 2019;Li et al, 2001;Khaspur et al, 2013;Sass et al, 2017;Rib et al, 2018; Table 3) shows that inflammatory and immune genes have increased as number and types, starting from reptiles (Boehm, 2012;Zimmerman et al, 2008). It has been suggested that, like in anurans (Harty et al, 2003;Mescher et al, 2016;Tsujioka et al, 2015), the high immune competence reached in amniotes eliminates every "embryonic-like" type of antigen, including those formed after wounding so that a regenerative blastema cannot form (Alibardi, 2015(Alibardi, , 2017b(Alibardi, , 2019d.…”

“…In most regenerative process so far described in mammals, some common signaling genes typical from anamniote regeneration are also activated, such as msx1 and bmp4 for mice digits (Han, Yang, Farrington, & Muneoka, 2003; Table 3). However, other signaling genes highly up‐regulated during anamniote regeneration are absent or low expressed during initial wound healing in amniote organs, in particular the Wnt members and non‐coding RNAs (Brant et al, 2019; Khaspur et al, 2013; Li et al, 2001; Rib et al, 2018; Sass et al, 2017; Table 3). While the wnt signaling pathway is highly up‐regulated for physiological regeneration of various tissues in mammals it appears reactivated only in the injured heart and other organs leading to scarring (Bastakoty & Young, 2016; Clevers, Loh, & Nusse, 2014; Whyte, Smith, & Helms, 2012).…”

Functional signatures in non-small-cell lung cancer: a systematic review and meta-analysis of sex-based differences in transcriptomic studies

“…A range of transcriptomic studies have described those biological processes contributing to the pathology of NSCLC or lung adenocarcinoma; however, technical variability among studies, inter-individual biological variability, and reduced sample size represent potential confounding factors in the evaluation of these contributions [13][14][15][16][17][18][19] . In addition, limited efforts have been made to explore the molecular mechanisms underlying sex-based differences in lung adenocarcinoma, with few studies considering this differential perspective [20,21] .…”