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正常および病理学的状態におけるマクロファージにおける Mafファミリー転写因子の機能の理解への貢献

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Contribution to understanding Maf family

transcription factors' functions in

macrophages in normal and pathological

conditions

著者

Dhouha Daassi

内容記述

この博士論文は内容の要約のみの公開(または一部

非公開)になっています

year

2017

その他のタイトル

正常および病理学的状態におけるマクロファージに

おける Mafファミリー転写因子の機能の理解への貢

学位授与大学

筑波大学 (University of Tsukuba)

学位授与年度

2016

報告番号

12102甲第8308号

URL

http://hdl.handle.net/2241/00147638

(2)

School of Integrative and Global Majors

Ph.D. Program in Human Biology (HBP)

論文概要

Dissertation Abstract

Purpose: The expression patterns of MafB and c-Maf in macrophage subtypes and tissue-resident macrophages have not been fully analyzed. On the other hand, macrophages are the main actor in many pathological cases, so we checked these proteins expression in ischemia renal disease (IRD). Materials and methods: wild type tissue-resident macrophages were subjected to immunohistochemistry using anti-MafB and anti-c-Maf. Data was confirmed by Flow cytometry (FACS) using Mafb/GFP knock-in heterozygous mice then in vitro analysis. Next, we induced acute kidney injury (AKI) by IRD and assessed by CRE/BUN level and histological analysis.

Result and discussion: Both MafB and c-Maf signals were observed in lymph node macrophages. In the splenic macrophages the MafB signal was detected, but the c-Maf signal was not. No expression of c-Maf or MafB was detected in macrophages in the lung and kidney. FACS analysis confirmed similar pattern. In vitro study showed that MafB expression was induced by IL-10 or IL-4 with IL-13 and was reduced by LPS or GM-CSF. But c-Maf expression was induced by IL-10 and reduced by IL-4 with IL-13 or GM-CSF. These results indicate that MafB and c-Maf have different expression patterns suggesting different functions in macrophages. This part of the thesis was published in March 2016 in BBRC journal. Whereas Previous reports did not show an obvious effect of MafB or c-Maf in ischemia renal disease (IRD), we found that kidney macrophages started to express MafB and c-Maf after 48h of IRD. More interestingly, the MafB cKO mice present high rate of loss of brush border and lack of macrophages and died after 48h from dIRD. This part of the thesis will be published as soon as it finishes (at maximum by April 2018).

Title of Doctor Dissertation: Contribution to understanding Maf family transcription factors’

functions in macrophages in normal and pathological conditions

(正常および病理学的状態におけるマクロファージにおける Maf ファミリー転写因子の機能の理解へ の貢献)

Last or Family Name First Middle

Daassi Dhouha

Student Number 201230512

Primary Academic Advisors

Affiliation: Biomedical sciences,Faculty of Medecine , Division of Anatomy and embryology

Name: Dr. Satoru Takahashi

Abstract

参照

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