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Enhancement effect of arachidonic acid-induced MT3-MMP expression on migration and skin wound healing of mesenchymal stem cell
아라키돈산에 의한 MT3-MMP 발현의 중간엽 줄기세포 이동 및 창상 치유능 증진 효과

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Authors
오상엽
Advisor
한호재
Major
수의과대학 수의학과
Issue Date
2018-02
Publisher
서울대학교 대학원
Keywords
arachidonic acidmesenchymal stem cellskin wound healingmigrationMT3-MMP
Description
학위논문 (석사)-- 서울대학교 대학원 : 수의과대학 수의학과, 2018. 2. 한호재.
Abstract
Arachidonic acid (AA) is largely released during injury, but it has not been fully studied yet how AA modulates wound repair with stem cells. Therefore, I investigated skin wound-healing effect of AA-stimulated human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in vivo and its molecular mechanism in vitro. I found that transplantation of hUCB-MSCs pre-treated with AA enhanced wound filling, re-epithelization, and angiogenesis in a mouse skin excisional wound model. AA significantly promoted hUCB-MSCs migration after a 24 h incubation, which was inhibited by the knockdown of G-protein-coupled receptor 40 (GPR40). AA activated mammalian target of rapamycin complex 2 (mTORC2) and Aktser473 through theGPR40/phosphoinositide 3-kinase (PI3K) signaling, which was responsible for the stimulation of an atypical protein kinase C (PKC) isoform, PKCζ. Subsequently, AA stimulated phosphorylation of p38 MAPK and transcription factor Sp1, and induced membrane type 3-matrix metalloproteinase (MT3-MMP)-dependent fibronectin degradation in promoting hUCB-MSCs motility. Finally, the silencing of MT3-MMP in AA-stimulated hUCB-MSCs failed to promote the repair of skin wounds owing to impaired cell motility. In conclusion, AA enhances skin wound healing through induction of hUCB-MSCs motility by MT3-MMP-mediated fibronectin degradation, which relies on GPR40-dependent mTORC2 signaling pathways.
Language
English
URI
https://hdl.handle.net/10371/142204
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Theses (Master's Degree_수의학과)
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