28 Apr Eczema and Psoriasis: Itch Linked to Specific Protein in Skin
MedicalResearch.com Interview with:
Santosh K. Mishra M.Tech., PhD
Assistant Professor of Neuroscience
Department of Molecular Biomedical Sciences
NC State Veterinary Medicine
Raleigh, NC 2760
MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by atopic dermatitis?
Response: Chronic allergic itch is a worldwide problem that leads to substantial health expenses,but what causes this universal urge to scratch remains elusive in chronic allergic itch. Atopic dermatitis is a common allergic skin disease that often associated with extremely itchy and inflamed skin.
In our study, we showed, for the first time, a molecular pathway that is involved in chronic allergic itch as we identified an endogenous mediator (periostin) and a new role for its sensory neuron receptor, the integrin αVβ3, which drives the excitability and transmission of itch signal to the spinal cord.
MedicalResearch.com: What are the main findings?
Response: In our study, we showed that an endogenous protein produced in the skin of atopic dermatitis and psoriasis, periostin, induces itch via its binding to integrin receptors on the sensory neurons in mice, dogs, and monkeys. We identified that the integrin receptor for periostin is expressed in a subset of TRPV1-expressing neurons. By using pharmacological and mouse genetics, we selectively inhibited integrin function and significantly reduced periostin-mediated itch behavior in mice.
We further identified the JAK/STAT pathway as a key regulator of the periostin released by keratinocytes. Lastly, we found that in chemical- and allergen-induced mouse models, there is an elevated level of periostin in the skin. Thus, our results revealed novel signaling mechanism linking the skin to sensory neurons and we further characterized the functional role of an integrin in dorsal root ganglia neurons for allergic itch
MedicalResearch.com: What should readers take away from your report?
Response: In this paper, we have reported, for the first time, a novel physiological system that mediates itch in the context of chronic allergic skin conditions such as atopic dermatitis. Altogether, our study shows a non-canonical role for integrins in sensory neuron excitability and the generation of itch behavior. Identifying the neuronal target is new in the itch field and this is just the beginning of our study, we still have a long way to go.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: Just like pain, itch is a worldwide problem with limited therapeutic options, a condition that negatively influences quality of life. In the future, we would like to investigate integrin receptor inhibitors in various complex disease models as potential therapeutics. In parallel, we would like to investigate the underpinnings of skin-neuronal axis in chronic itch conditions.
MedicalResearch.com: Is there anything else you would like to add? Any disclosures?
Response: This study were supported by NCSU startup funds to Dr. Mishra and NIH grant (AR-064456) to M.C.K to support NHP study.A private gift provided by Dr. John M. Davis supported a graduate scholarship for J.J.W.
Periostin Activation of Integrin Receptors on Sensory Neurons Induces Allergic Itch.Mishra SK, Wheeler JJ, Pitake S, Ding H, Jiang C, Fukuyama T, Paps JS, Ralph P, Coyne J, Parkington M, DeBrecht J, Ehrhardt-Humbert LC, Cruse GP, Bäumer W, Ji RR, Ko MC, Olivry T. Cell Rep. 2020 Apr 7;31(1):107472. doi: 10.1016/j.celrep.2020.03.036.
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