VDUP1 Ameliorate Fibrogenesis in The Liver Following CCl4 by Inbiting Hepatic Inflammation and Tnf-α Expression
- 주제(키워드) VDUP1 , Liver , Fibrosis
- 발행기관 고려대학교 대학원
- 지도교수 박세호
- 발행년도 2014
- 학위수여년월 2014. 2
- 학위구분 석사
- 학과 일반대학원 생명과학과
- 세부전공 분자생물학전공
- 원문페이지 60 p
- 실제URI http://www.dcollection.net/handler/korea/000000048385
- 본문언어 영어
- 제출원본 000045793053
초록/요약
Abstract Hepatic fibrosis represents the generalized response of the liver to injury and is characterized by excessive deposition of extracellular matrix. Here, we investigated the role of the Vitamin D3 up-regulated protein 1 (VDUP1) in a carbon tetrachloride (CCl4)–induced hepatic fibrosis model. After chronic CCl4 treatment, liver fibrosis was significantly accelerated in VDUP1 knockout(KO) mice compared with wild-type(WT) mice, assessed by α-SMA immunostaining, Sirius red staining, and mRNA expression levels of α-SMA, Col1α(I), TGF-β1, TIMP-1, and MMP9. A single injection of CCl4 in VDUP1 KO mice increased liver damage than in WT mice with the enhanced expression of α-SMA, Col1α(I), TGF-β1, and TIMP-1. In addition, VDUP1 KO mice showed significant elevations in inflammatory cell recruitment and cytokine production, including TNF-α, MCP-1, and MIP-1β versus WT mice. Finally, macrophage depletion or TNF-α neutralization significantly reduced the expression of α-SMA, TGF-β1, Col1α(I), and TIMP-1 in VDUP1 KO mice. In conclusion, these results represent that VDUP1 inhibits hepatic inflammation and TNF-α expression, thereby ameliorating fibrogenesis in the liver following CCl4.
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CONTENTS I
LIST OF FIGURES Ⅲ
ABSTRACT V
INTRODUCTION 1
MATERIALS AND METHODS 4
RESULTS 9
1.Hepatic fibrosis was increased in VDUP1 KO mice following repeated CCl4 injections 9
2.Deficiency of VDUP1 increases infiltration of macrophages at the site of injury and elevates the mRNA expression levels associated with liver fibrosis in chronic damage model 15
3.The liver injury was exacerbated in VDUP1 KO mice than WT mice following single injection of CCl4 20
4.The activation of HSCs was more increased in VDUP1 KO mice than WT mice by a single injection of CCl4 21
5.VDUP1 inhibits infiltration of macrophages and expression of mRNA associated with hepatic fibrogenesis 25
6.Depletion of macrophages reduces hepatic fibrogenesis 28
7.Neutralization of TNF-α reduces damage and activation of HSCs 34
8.Neutralization of TNF-α reduces infiltration of macrophages and mRNA expression levels associated with hepatic fibrogenesis in VDUP1 KO mice 39
DISCUSSION 42
REFERENCES 46
ABSTRAC in KOREAN 51
