Study on macrophage NAMPT function in inflammation-induced colon cancer
- 주제(키워드) NAMPT , Macrophage , Phagocytosis , Colitis , Colitis-associated cancer
- 주제(DDC) 570
- 발행기관 아주대학교
- 지도교수 김유선
- 발행년도 2023
- 학위수여년월 2023. 2
- 학위명 석사
- 학과 및 전공 일반대학원 의생명과학과
- 실제URI http://www.dcollection.net/handler/ajou/000000032677
- 본문언어 한국어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
목차
I. INTRODUCTION 1
II. MATERIALS AND METHODS 4
A. Antibodies and chemical reagents 4
B. Mice 4
C. Cell culture 5
D. DSS-induced colitis model 5
E. AOM/DSS-induced colorectal cancer model 5
F. Xenograft model 6
G. Isolation of colon lamina propria cells 6
H. Flow cytometric analysis 7
I. Immunoblot analysis 7
J. Immunohistochemistry analysis 7
K. RNA isolation and qRT-PCR 8
L. Phagocytosis measurement 8
M. Efferocytosis measurment 8
N. Measurment of NAD, NADPH 8
O. Cell proliferation assay 9
P. Wound healing assay 9
III. RESULTS 10
A. Loss of NAMPT in macrophages enhances DSS-induced colitis 10
B. NAMPT deletion impairs the resolution of inflammation in the DSS-treated colon 12
C. NAMPT expression in macrophages is essential for optimal phagocytic activity 16
D. NAMPT increases NADPH levels 20
E. Colitis-induced colorectal tumor progression is downregulated in macrophage-specific NAMPT-deleted mice 22
F. Anti-tumor immunity activated in colitis-induced colorectal tumor tissues from macrophage-specfic NAMPT deleted mice 25
G. NAMPT in macrophages affects colon cancer progression 27
H. Deletion of NAMPT shows failure in sufficient elimination of apoptotic cells in TME 30
I. Defective efferocytotic activity in macrophages leads to polarization in M1-like macrophages 36
J. NAMPT-deleted macropahges enhance tumor cell killing by leading polarization to M1-like macrophages 39
K. NAMPT deficiency triggers STING-dependent type I IFN response by impairing efferocytosis 41
L. Extracellular NAMPT promotes the proliferation of colon cancer cells 45
IV. DISCUSSION 48
V. REFERENCES 50
국문요약 54