Limb Regeneration in Amphibians: Immunological Considerations

Mescher, Anthony L.; Neff, Anton W.

doi:10.1100/tsw.2006.323

Cited by 66 publications

(64 citation statements)

References 67 publications

(78 reference statements)

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“…Microarray and other gene expression studies suggest that proteins involved in immune defense and other aspects of inflammation are particularly important in the post-amputation regenerative response of amphibian limbs (Harty et al, 2003;Grow et al, 2006;Mescher and Neff, 2006). Similar results are reported in other regenerating systems (Putta et al, 2004;Lien et al, 2006; Fig.…”

Section: Proteins With Immune Functionsupporting

confidence: 76%

“…Up-regulation of many such inflammationrelated genes is greater in limbs of prometamorphic Xenopus at regeneration-incomplete stages than in limbs at stage 53, which regenerate well (Grow et al, 2006). One interpretation of these results is that the developmental state of the anuran immune system and the differentiation status and number of cells mediating the inflammatory response to trauma may determine the nature of the regenerative response to amputation (Harty et al, 2003;Mescher and Neff, 2005;Mescher and Neff, 2006), a hypothesis consistent with current work on scar formation after injury to developing mammalian skin (Martin and Leibovich, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…Thrombin and tissue factor (which is involved in conversion of prothrombin to thrombin) have been shown to be important for dedifferentiation of muscle fibers in regenerating limbs (Kumar et al, 2004) and pigmented epithelial cells in lens regeneration (Imokawa et al, 2004). These and other aspects of immune involvement in regeneration have recently been reviewed (Godwin and Brockes, 2006;Mescher and Neff, 2006).…”

Section: Introductionmentioning

confidence: 99%

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Proteomics analysis of regenerating amphibian limbs: changes during the onset of regeneration

2009

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During amphibian epimorphic limb regeneration, local injury produces metabolic changes that lead to cellular dedifferentiation and formation of a blastema, but few details of these changes have been elucidated. Here we report the first global proteomic analysis of epimorphic regeneration comparing the profiles of abundant proteins in larval limbs of the anuran Xenopus laevis (stage 53) at the time of amputation (0dPA) and 3 days post-amputation when the regeneration blastema is developing (3dPA). We identified and quantified 1517 peptides, of which 1067 were identified with high peptide ID confidence. Of these 1067 proteins, 489 showed significant changes in quantity between the two groups. Taking into account identical peptides whose fold changes were within 20%, and not including peptides whose fold changes were below the observed fold changes of peptides for the internal standard (chicken lysozyme), we were able to identify 145 peptides elevated in 3dPA relative to 0dPA and 220 peptides in 0dPA relative to 3dPA. In this report, we focus on those proteins that were elevated in the 3dPA tissue relative to 0dPA. In this class were members of the annexin family (e.g. ANXA1, ANXA2, ANXA5) and the ANXA2-binding partner S100A10, which have important immunoregulatory roles in other systems and were also shown to be differentially expressed in stage 53 and 57 3dPA and 5dPA blastemas in our previous microarray studies. Besides elucidating the possible modulation of inflammation during amphibian limb regeneration, our proteomic study also provides insight into dedifferentiation by revealing up-regulation of proteins known to characterize many stem cells.

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Section: Proteins With Immune Functionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Proteomics analysis of regenerating amphibian limbs: changes during the onset of regeneration

2009

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“…Salamanders are also able to perform scar-free repair of deep tissue wounds after injury (8). Although the cellular mediators and immunological signaling necessary for regeneration in the salamander have not been described, recent reports suggest that inflammation may influence the initiation and completion of wound healing and regeneration (9)(10)(11)(12)(13)(14), as the cytokine microenvironment directly influences the time course of leukocyte infiltration, cellular proliferation, angiogenesis, and collagen remodeling of damaged tissues.…”

mentioning

confidence: 99%

Macrophages are required for adult salamander limb regeneration

Godwin

Pinto

Rosenthal

2013

Proc. Natl. Acad. Sci. U.S.A.

719

767

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The failure to replace damaged body parts in adult mammals results from a muted growth response and fibrotic scarring. Although infiltrating immune cells play a major role in determining the variable outcome of mammalian wound repair, little is known about the modulation of immune cell signaling in efficiently regenerating species such as the salamander, which can regrow complete body structures as adults. Here we present a comprehensive analysis of immune signaling during limb regeneration in axolotl, an aquatic salamander, and reveal a temporally defined requirement for macrophage infiltration in the regenerative process. Although many features of mammalian cytokine/chemokine signaling are retained in the axolotl, they are more dynamically deployed, with simultaneous induction of inflammatory and anti-inflammatory markers within the first 24 h after limb amputation. Systemic macrophage depletion during this period resulted in wound closure but permanent failure of limb regeneration, associated with extensive fibrosis and disregulation of extracellular matrix component gene expression. Full limb regenerative capacity of failed stumps was restored by reamputation once endogenous macrophage populations had been replenished. Promotion of a regeneration-permissive environment by identification of macrophage-derived therapeutic molecules may therefore aid in the regeneration of damaged body parts in adult mammals.

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“…Urodele amphibians, due to their robust capacity to regenerate a wide variety of tissues, including spinal cord, brain, limb, retina, and lens, have historically been a key model system driving regeneration research [16][17][18]. Unlike adult mammalian cardiomyocytes, newt cardiomyocytes will readily undergo proliferation in tissue culture, thus representing one possible key difference that reflects regenerative capacity [19,20].…”

Section: Mammalian and Amphibian Heart Regenerationmentioning

confidence: 99%

Zebrafish heart regeneration as a model for cardiac tissue repair

Major

Poss

2007

Drug Discovery Today: Disease Models

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Heart disease remains the leading cause of mortality throughout the world. Mammals have an extremely limited capacity to repair lost or damaged heart tissue, thus encouraging biologists to seek out models for heart regeneration. Zebrafish exhibit a robust regenerative capacity in a variety of tissues including the fin, spinal cord, retina, and heart, making it the sole regenerative vertebrate organism currently amenable to genetic manipulation. Future studies will utilize functional approaches to tease apart zebrafish heart regeneration in hopes of unlocking our own regenerative potential.

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Limb Regeneration in Amphibians: Immunological Considerations

Cited by 66 publications

References 67 publications

Proteomics analysis of regenerating amphibian limbs: changes during the onset of regeneration

Proteomics analysis of regenerating amphibian limbs: changes during the onset of regeneration

Macrophages are required for adult salamander limb regeneration

Zebrafish heart regeneration as a model for cardiac tissue repair

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