A novel peptide derived from fibroblast growth factor modulates the mitogen activated protein kinase pathway and mediates fibroblast migration in wound healing
- 주제(키워드) Fibroblast growth factor 2 , Peptide , Wound healing , Full agonist , Fibroblast growth factor signaling
- 주제(DDC) 547
- 발행기관 아주대학교
- 지도교수 최상돈
- 발행년도 2023
- 학위수여년월 2023. 8
- 학위명 석사
- 학과 및 전공 일반대학원 분자과학기술학과
- 실제URI http://www.dcollection.net/handler/ajou/000000033078
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Fibroblast growth factors (FGFs) are a large family of growth factors and cell-signaling proteins that act through tyrosine kinase receptors known as FGF receptors (FGFRs). bFGF, also known as basic FGF, regulates diverse functions such as cell development, repair, and metabolism. bFGF upon binding with FGFR, phosphorylates tyrosine residues of FGFR by bFGF, activates the phospholipase C gamma, phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B, and mitogen-activated protein kinase pathways to induce the release of cytokines. These cytokines trigger cell proliferation, differentiation, and migration. In this study, we designed three bFGF agonistic peptides and their agonistic effect was checked in comparison to bFGF. Among the three designed peptides, F3 peptide showed the best activity. F3 induced cell proliferation in a similar fashion to bFGF. Treatment of human breast cancer cells with F3 resulted in the phosphorylation of FGFR. When F3 was co-treated with bFGF, bFGF didn’t decrease the phosphorylation level of FGFR, which confirmed the F3 peptide is full agonist of bFGF. F3 also activated the downstream signaling proteins including mitogen activated protein kinases. In the in-vitro wound healing assay, F3 demonstrated wound healing effect which was inhibited when F3 was co-treated with Erdafitinib, which shows that F3 specifically activates FGFR. Through surface plasmon resonance analysis it was confirmed that F3 binds specifically with FGFR in a concentration dependent manner. In conclusion, F3 is functional agonist specific to FGFR and seems to have therapeutic effects in wound healing.
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