Wounds increase activin in skin and a vasoactive neuropeptide in sensory ganglia

Document Type

Journal Article

Publication Date

7-1-2004

Journal

Developmental Biology

Volume

271

Issue

1

DOI

10.1016/j.ydbio.2004.04.003

Keywords

Activin; Bone morphogenetic protein; Calcitonin gene-related peptide; Dorsal root ganglion; Sensory neuron; Skin wound; Smad; Target-derived; Transforming growth factor β

Abstract

Successful healing of skin wounds requires sensory innervation and the release of vasoactive neuropeptides that dilate blood vessels and deliver serum proteins to the wound, and that cause pain that protects from further injury. Activin has been proposed as a target-derived regulator of sensory neuropeptides during development, but its role in the mature nervous system is unknown. While adult skin contains a low level of activin, protein levels in skin adjacent to a wound increase rapidly after an excision. Neurons containing the neuropeptide calcitonin gene-related peptide (CGRP) increased in sensory ganglia that projected to the wounded skin, but not in ganglia that projected to unwounded skin, suggesting that neurons respond to a local skin signal. Indeed, many adult sensory neurons respond with increased CGRP expression to the application of activin in vitro and utilize a smad-mediated signal transduction pathway in this response. A second skin-derived factor nerve growth factor (NGF) also increased in wounded skin and increased CGRP in cultured adult dorsal root ganglia (DRG) neurons but with lower efficacy. Together, these data support the hypothesis that activin made by skin cells regulates changes in sensory neuropeptides following skin injury, thereby promoting vasodilation and wound healing. © 2004 Elsevier Inc. All rights reserved.

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