The role of myokine in pruritus-associated skin disorder
가려움증이 동반된 피부질환에 있어서 마이오카인의 역할 규명
- 주제(키워드) Myokine , Inflammation , Neurosensory response , Leukemia inhibitory factor , Dorsal root ganglion neuron
- 발행기관 고려대학교 대학원
- 지도교수 유임주
- 발행년도 2020
- 학위수여년월 2020. 2
- 학위구분 박사
- 학과 대학원 의과학과
- 세부전공 의생명과학전공
- 원문페이지 37 p
- UCI I804:11009-000000126681
- DOI 10.23186/korea.000000126681.11009.0000944
- 본문언어 영어
- 제출원본 000046028459
초록/요약
Certain myokines are associated with inflammation and can mediate cross-talk between skin and muscle. The impaired skin barrier function induced by peripheral inflammation could trigger abnormal muscle contraction leading to an increased neurosensory response and neurogenic inflammation. This study verified whether the specific myokine, leukemia inhibitory factor (LIF), can have meaningful effects on the aggravation of inflammatory skin disorders and examine the underlying molecular mechanisms. The hypothesis was developed by finding that both of LIF and its receptors are found in neural tissues and LIF could mediate muscle-brain interaction through activation of signaling pathways in dorsal root ganglion (DRG) neurons. An in vitro coculture model between DRG neurons and keratinocytes was used to assess possible trophic effects on axonal growth by LIF. LIF treatment to DRG neurons showed significant neurite outgrowth. LIF also meaningfully affected axonal growth in the coculture model. LIF application resulted in increased tropomyosin receptor kinase A (TrkA), protein phosphatase 2A alpha (PP2Aα), p38 mitogen-activated protein kinase and Akt phosphorylation in DRG neurons. Furthermore, LIF could induce dissociation between TrkA and PP2Aα. Lastly, Akt phosphorylation by LIF in DRG neurons was effectively prohibited with TrkA inhibitor, K252a. LIF, resulting from abnormal muscle contraction, has roles in the development of an increased neurosensory response and neurogenic inflammation via increased neurite outgrowth and activation of serial signaling pathways in DRG neurons.
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ABSTRACT........................................................................................ⅰ
CONTENTS.......................................................................................ⅲ
LIST OF FIGURES...............................................................................ⅳ
ABBREVIATIONS...............................................................................ⅴ
1. BACKGROUND..............................................................................1
2. MATERIALS AND METHODS..........................................................4
3. RESULTS........................................................................................8
3.1. The effect of LIF on neurite outgrowth in DRG neurons.............8
3.2. The effect of LIF on neurite outgrowth in compartmented
coculture systems between DRG neurons and NHEKs................8
3.3. LIF signaling in DRG neurons regarding p38 MAPK and Akt.......9
3.4. LIF signaling in DRG neurons including TrkA and PP2Aα.............9
3.5. The effect of TrkA inhibition on LIF signaling in DRG neurons...10
4. DISCUSSION.................................................................................11
5. REFERENCES................................................................................14
