Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 9415 - 9420 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences |
| Volume | 110 |
| Issue number | 23 |
| DOIs | |
| Publication status | Published - 2013 |
Cite this
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Macrophages are required for adult salamander limb regeneration. / Godwin, James Walter; Pinto, Ruvantha Ignatius Alexander; Rosenthal, Nadia Alicia.
In: Proceedings of the National Academy of Sciences, Vol. 110, No. 23, 2013, p. 9415 - 9420.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Macrophages are required for adult salamander limb regeneration
AU - Godwin, James Walter
AU - Pinto, Ruvantha Ignatius Alexander
AU - Rosenthal, Nadia Alicia
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
UR - http://www.pnas.org/content/early/2013/05/17/1300290110.full.pdf
U2 - 10.1073/pnas.1300290110
DO - 10.1073/pnas.1300290110
M3 - Article
VL - 110
SP - 9415
EP - 9420
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 23
ER -