The ability to regenerate cutaneous sensory axons in response to injury is crucial for restoring tissue function. Despite its importance and many research efforts in the past, the mechanisms for cutaneous axon regeneration following injury have remained elusive. We have previously discovered that the small reactive oxygen species hydrogen peroxide (H2O2) is a key regulatory molecule for stimulating cutaneous axon growth. Historically, H2O2 has been seen as a cell-damaging molecule, when present at high concentrations in cells. Recent work however, demonstrates that low, non-toxic concentrations of H2O2 are important for regulation of many cellular functions. This is achieved by the oxidation of redox-sensitive cysteine residues in signaling proteins, most notably of kinases, phosphatases, and transcription factors, which alters their structure and function. As the research field of H2O2 signaling is relatively new, insight into its signaling properties during tissue repair is only beginning to emerge. The significance of this proposal is that it will elucidate mechanisms utilized by injury-induced H2O2 that stimulate cutaneous axon regeneration. The insight gained from this research will aid in the development of treatments for damaged axons due to disease or trauma. Our approach is to combine in vivo imaging and parallel deep sequencing of miRNAs and mRNAs to analyze H2O2 responsive genetic networks in somatosensory neurons that are essential for stimulating axon regeneration.

Public Health Relevance

The goal of this project is to understand how hydrogen peroxide promotes the natural repair and regeneration of cutaneous somatosensory axons. The project is relevant to public human health because cutaneous axon damage, such as in peripheral neuropathy or trauma, significantly impacts sensory function and wound healing. This research will further reveal fundamental principles of hydrogen peroxide signaling in wounds and lay the groundwork for future investigations of axon repair in disease models.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory Grants (P20)
Project #
1P20GM104318-01
Application #
8465640
Study Section
Special Emphasis Panel (ZGM1-TWD-B (CB))
Project Start
Project End
Budget Start
2013-09-01
Budget End
2014-05-31
Support Year
1
Fiscal Year
2013
Total Cost
$323,183
Indirect Cost
$131,013
Name
Mount Desert Island Biological Lab
Department
Type
DUNS #
077470003
City
Salsbury Cove
State
ME
Country
United States
Zip Code
04672
Lee, Bum-Kyu; Uprety, Nadima; Jang, Yu Jin et al. (2018) Fosl1 overexpression directly activates trophoblast-specific gene expression programs in embryonic stem cells. Stem Cell Res 26:95-102
Hampton, Thomas H; Jackson, Craig; Jung, Dawoon et al. (2018) Arsenic Reduces Gene Expression Response to Changing Salinity in Killifish. Environ Sci Technol 52:8811-8821
Yin, Viravuth P (2018) In Situ Detection of MicroRNA Expression with RNAscope Probes. Methods Mol Biol 1649:197-208
King, Benjamin L; Rosenstein, Michael C; Smith, Ashley M et al. (2018) RegenDbase: a comparative database of noncoding RNA regulation of tissue regeneration circuits across multiple taxa. NPJ Regen Med 3:10
Lavine, Kory J; Pinto, Alexander R; Epelman, Slava et al. (2018) The Macrophage in Cardiac Homeostasis and Disease: JACC Macrophage in CVD Series (Part 4). J Am Coll Cardiol 72:2213-2230
Yamada, Toshiki; Strange, Kevin (2018) Intracellular and extracellular loops of LRRC8 are essential for volume-regulated anion channel function. J Gen Physiol 150:1003-1015
Waldron, Ashley L; Schroder, Patricia A; Bourgon, Kelly L et al. (2018) Oxidative stress-dependent MMP-13 activity underlies glucose neurotoxicity. J Diabetes Complications 32:249-257
Beck, Samuel; Rhee, Catherine; Song, Jawon et al. (2018) Implications of CpG islands on chromosomal architectures and modes of global gene regulation. Nucleic Acids Res 46:4382-4391
Andralojc, Karolina M; Campbell, Anne C; Kelly, Ashley L et al. (2017) ELLI-1, a novel germline protein, modulates RNAi activity and P-granule accumulation in Caenorhabditis elegans. PLoS Genet 13:e1006611
Godwin, James W; Pinto, Alexander R; Rosenthal, Nadia A (2017) Chasing the recipe for a pro-regenerative immune system. Semin Cell Dev Biol 61:71-79

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