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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
- Advisor
- 한호재
- Major
- 수의과대학 수의학과
- Issue Date
- 2018-02
- Publisher
- 서울대학교 대학원
- Keywords
- arachidonic acid ; mesenchymal stem cell ; skin wound healing ; migration ; MT3-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
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