Induction of Timp1 in Smooth Muscle Cells during Development of Abdominal Aortic Aneurysms

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Induction of Timp1 in Smooth Muscle Cells during Development of Abdominal Aortic Aneurysms

Material type: 博士論文

Author: Bumdelger, Batmunkh

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Name of awarding university/degree: 広島大学(Hiroshima University),博士(医学)

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Note (General)：: type:textAbdominal aortic aneurysm (AAA) is known to develop mainly by the increased diameter of aorta through metalloproteinases (MMPs). Although act...

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Material Type: 博士論文
Title: Induction of Timp1 in Smooth Muscle Cells during Development of Abdominal Aortic Aneurysms
Author/Editor: Bumdelger, Batmunkh
Author Heading: Bumdelger, Batmunkh
Alternative Title: 腹部大動脈瘤形成における、平滑筋細胞でのTimp1遺伝子誘導
Degree grantor/type: 広島大学(Hiroshima University)
Date Granted: 2013-09-25
Dissertation Number: 甲第6246号
Degree Type: 博士(医学)
Text Language Code: eng
Subject Heading: Abdominal aortic aneurysm
Mmp9
Timp1
TNF-α
NDC: 490
Target Audience: 一般
Note (General): type:text
Abdominal aortic aneurysm (AAA) is known to develop mainly by the increased diameter of aorta through metalloproteinases (MMPs). Although activities of MMPs are tightly regulated by the presence of tissue inhibitor of MMPs (TIMPs) and imbalances between MMPs and TIMPs may serve to fragility of arterial wall, little is known about TIMPs behavior in aneurysmal formation. Here, we utilized a murine experimental AAA model, and found that by immunohistochemical analysis, Timp1 as and Timp1 mRNA levels was also revealed in aortic tissue in AAA by RT-PCR. In cultured vascular smooth muscle cells (SMCs), Tumor Necrosis Factor (TNF)-α significantly activated both Mmp9 and Timp1 expression, and they were blocked by Jun kinase inhibitor (SP600125) in a dose-dependent manner. Interestingly, a proteasome inhibitor (MG132), which is known as an agent for inhibition of the nuclear factor-kappa B (NF-kB), significantly inhibited the TNF-α-induced expression of Timp1, whereas MG132, which also works as an activator of c-Jun/AP-1 pathway, strongly increased Mmp9. Taken together, inflammatory cytokines, including TNF-α, may simultaneously induce MMPs and TIMPs for the remodeling of the medial layer, leading to the increased diameter of the aorta, the aneurysm.
Format (IMT): application/pdf
Source: fulltext
https://ir.lib.hiroshima-u.ac.jp/files/public/3/36323/20141125043110267594/k6246_3.pdf
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https://ir.lib.hiroshima-u.ac.jp/files/public/3/36323/20181120132556441625/k6246_1.pdf
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https://ir.lib.hiroshima-u.ac.jp/files/public/3/36323/20181120132556827899/k6246_2.pdf
Access Restrictions: インターネット公開
Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）
https://irdb.nii.ac.jp
Original Data Provider (Database): 広島大学 : 広島大学学術情報リポジトリ