The recently elucidated proresolving conjugates in tissue regeneration (CTR) maresin-CTR (MCTR), protectin-CTR (PCTR), and resolvin-CTR (RCTR), termed cysteinyl-specialized proresolving mediators (cys-SPMs) each promotes regeneration, controls infection, and accelerates resolution of inflammation. Here, we sought evidence for cys-SPM activation of primordial pathways in planaria () regeneration that might link resolution of inflammation and regeneration. On surgical resection, planaria regeneration was enhanced with MCTR3, PCTR3, or RCTR3 (10 nM), each used for RNA sequencing. The three cys-SPMs shared up-regulation of 175 known transcripts with fold-change > 1.25 and combined false discovery rate (FDR) < 0.002, and 199 canonical pathways (FDR < 0.25), including NF-κB pathways and an ortholog of human TRAF3 (TNFR-associated factor 3). Three separate pathway analyses converged on TRAF3 up-regulation by cys-SPMs. With human macrophages, three cys-SPMs each dose-dependently increased TRAF3 expression in a cAMP-PKA-dependent manner. TRAF3 overexpression in macrophages enhanced Interleukin-10 (IL-10) and phagocytosis of IL-10 also increased phagocytosis in a dose-dependent manner. Silencing of mouse TRAF3 in vivo significantly reduced IL-10 and macrophage phagocytosis. TRAF3 silencing in vivo also relieved cys-SPMs' actions in limiting polymorphonuclear neutrophil in exudates. These results identify cys-SPM-regulated pathways in planaria regeneration, uncovering a role for TRAF3/IL-10 in regulating mammalian phagocyte functions in resolution. Cys-SPM activation of TRAF3 signaling is a molecular component of both regeneration and resolution of infectious inflammation.
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http://dx.doi.org/10.1073/pnas.2013374118 | DOI Listing |
The activation of progenitor cells near wound sites is a common feature of regeneration across species, but the conserved signaling mechanisms responsible for this step in whole-body regeneration are still incompletely understood. The acoel undergoes whole-body regeneration using Piwi+ pluripotent adult stem cells (neoblasts) that accumulate at amputation sites early in the regeneration process. The EGFR signaling pathway has broad roles in controlling proliferation, migration, differentiation, and cell survival across metazoans.
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January 2025
College of Life Science, Henan Normal University, No. 46, Jianshe Road, Xinxiang 453007, Henan, China.
Sox genes encode a family of transcription factors that regulate multiple biological processes during metazoan development, including embryogenesis, tissue homeostasis, nervous system specification, and stem cell maintenance. The planarian Dugesia japonica contains a reservoir of stem cells that grow and divide continuously to support cellular turnover. However, whether SOX proteins retain these conserved functions in planarians remains to be determined.
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December 2024
College of Life Science, Henan Normal University, Xinxiang 453007, China. Electronic address:
The widespread application of quantum dots (QDs) in recent years has raised concerns about potential environmental and human health risks. Although the toxicity of cadmium telluride quantum dots (CdTe QDs) has been partially studied, their effects on stem cells, tissue regeneration, neurodevelopment, and neurobehavioral toxicity remain unclear. This study aimed to investigate the combined toxic effects and mechanisms of CdTe QDs on planarians at the individual, tissue, cellular, and molecular levels.
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January 2025
Departamento de Zoologia, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.
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View Article and Find Full Text PDFMethods Mol Biol
January 2025
West Virginia University, Morgantown, WV, USA.
Hox genes are highly conserved developmental regulators instrumental to the formation of a wide range of diverse body plans across metazoans. While significant progress in the field of Hox gene research has been made, persistent challenges in unraveling their mechanisms of action and full repertoire of functions remain. To date, investigations of Hox gene function have been primarily conducted in research models belonging to ecdysozoa and vertebrata.
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