Hydrogen peroxide promotes injury-induced peripheral sensory axon regeneration in the zebrafish skin.
Hydrogen peroxide promotes injury-induced peripheral sensory axon regeneration in the zebrafish skin.
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DOI:
10.1371/journal.pbio.1000621
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发表时间:
2011-05
期刊:
影响因子:
9.8
通讯作者:
Sagasti A
中科院分区:
文献类型:
--
作者:
Rieger S;Sagasti A
Production of H2O2 by injured zebrafish skin cells promotes the regeneration of nearby somatosensory axon terminals, thus coordinating wound healing of the skin with sensory reinnervation. Functional recovery from cutaneous injury requires not only the healing and regeneration of skin cells but also reinnervation of the skin by somatosensory peripheral axon endings. To investigate how sensory axon regeneration and wound healing are coordinated, we amputated the caudal fins of zebrafish larvae and imaged somatosensory axon behavior. Fin amputation strongly promoted the regeneration of nearby sensory axons, an effect that could be mimicked by ablating a few keratinocytes anywhere in the body. Since injury produces the reactive oxygen species hydrogen peroxide (H2O2) near wounds, we tested whether H2O2 influences cutaneous axon regeneration. Exposure of zebrafish larvae to sublethal levels of exogenous H2O2 promoted growth of severed axons in the absence of keratinocyte injury, and inhibiting H2O2 production blocked the axon growth-promoting effects of fin amputation and keratinocyte ablation. Thus, H2O2 signaling helps coordinate wound healing with peripheral sensory axon reinnervation of the skin. Touch-sensing neurons project axonal processes that branch extensively within the outer layers of skin to detect touch stimuli. Recovering from skin injuries thus requires not only repair of damaged skin tissue but also regeneration of the sensory axons innervating it. To study whether skin wound healing is coordinated with sensory innervation, we compared the regeneration of severed sensory axons innervating larval zebrafish tail fins with and without concomitant injury to surrounding skin cells. Severed axons regenerated more robustly when nearby skin cells were also damaged, suggesting that wounded skin releases a short-range factor that promotes axon growth. The reactive oxygen species hydrogen peroxide (H2O2) is known to be produced by injured cells, making it a candidate for mediating this signal. We found that adding exogenous H2O2 improved the regeneration of severed axons. Conversely, blocking H2O2 production prevented the axon growth-promoting effect of skin injury. Thus, H2O2 promotes axon growth after skin damage, helping to ensure that healing skin is properly innervated.
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影响因子:
14.8
作者:
Iovine, M. Katryn
通讯作者:
Iovine, M. Katryn
影响因子:
2.5
作者:
Kawakami, A;Fukazawa, T;Takeda, H
通讯作者:
Takeda, H
DOI:
10.3791/1129
发表时间:
2009-02-16
期刊:
Journal of visualized experiments : JoVE
影响因子:
--
作者:
O'Brien, Georgeann S;Rieger, Sandra;Sagasti, Alvaro
通讯作者:
Sagasti, Alvaro
影响因子:
2.7
作者:
Endo, T;Bryant, SV;Gardiner, DM
通讯作者:
Gardiner, DM
影响因子:
2.7
作者:
Harsum, S;Clarke, JDW;Martin, P
通讯作者:
Martin, P