PMID- 24279124
OWN - NLM
STAT- MEDLINE
DCOM- 20131218
LR  - 20161128
IS  - 0018-2052 (Print)
IS  - 0018-2052 (Linking)
VI  - 62
IP  - 3
DP  - 2013 Sep
TI  - Induction of Timp1 in smooth muscle cells during development of abdominal aortic 
      aneurysms.
PG  - 63-7
AB  - 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)-alpha 
      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-kappaB), significantly inhibited the TNF-alpha-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-alpha, may simultaneously induce MMPs and TIMPs for the 
      remodeling of the medial layer, leading to the increased diameter of the aorta, 
      the aneurysm.
FAU - Bumdelger, Batmunkh
AU  - Bumdelger B
AD  - Department of Cardiovascular Physiology and Medicine, Graduate School of 
      Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
FAU - Kokubo, Hiroki
AU  - Kokubo H
FAU - Kamata, Ryo
AU  - Kamata R
FAU - Fujii, Masayuki
AU  - Fujii M
FAU - Ishida, Mari
AU  - Ishida M
FAU - Ishida, Takafumi
AU  - Ishida T
FAU - Yoshizumi, Masao
AU  - Yoshizumi M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Japan
TA  - Hiroshima J Med Sci
JT  - Hiroshima journal of medical sciences
JID - 0421060
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Timp1 protein, mouse)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - EC 3.4.24.35 (Mmp9 protein, mouse)
RN  - M4I0D6VV5M (Calcium Chloride)
SB  - IM
MH  - Animals
MH  - Aorta, Abdominal/metabolism
MH  - Aortic Aneurysm, Abdominal/chemically induced/genetics/*metabolism
MH  - Calcium Chloride
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Muscle, Smooth, Vascular/drug effects/*metabolism
MH  - Myocytes, Smooth Muscle/drug effects/*metabolism
MH  - Protein Kinase Inhibitors/pharmacology
MH  - RNA, Messenger/metabolism
MH  - Tissue Inhibitor of Metalloproteinase-1/genetics/*metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Up-Regulation
EDAT- 2013/11/28 06:00
MHDA- 2013/12/19 06:00
CRDT- 2013/11/28 06:00
PHST- 2013/11/28 06:00 [entrez]
PHST- 2013/11/28 06:00 [pubmed]
PHST- 2013/12/19 06:00 [medline]
PST - ppublish
SO  - Hiroshima J Med Sci. 2013 Sep;62(3):63-7.