Transcriptional regulation of inflammatory and extracellular matrix-regulating genes in experimental subarachnoid cerebral arteries following hemorrhage in rats
(2007) In Journal of Neurosurgery 107(5). p.1015-1022- Abstract
- Object. Subarachnoid hemorrhage (SAH) results in the expression of inflammatory and extracellular matrix (ECM)related genes and various G protein-coupled receptors. In the present study, the authors evaluated the time course and sequence of the transduction pathways, p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase-1 and 2 (ERK1/2), and associated transcription factor activation as well as gene regulation and associated protein levels. Methods. Subarachnoid hemorrhage was induced in rats by injecting 250 mu l of blood into the suprachiasmatic cistern, and gene regulation in the cerebral arteries was examined at various points in time following SAH by using quantitative polymerase chain reaction (PCR)... (More)
- Object. Subarachnoid hemorrhage (SAH) results in the expression of inflammatory and extracellular matrix (ECM)related genes and various G protein-coupled receptors. In the present study, the authors evaluated the time course and sequence of the transduction pathways, p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase-1 and 2 (ERK1/2), and associated transcription factor activation as well as gene regulation and associated protein levels. Methods. Subarachnoid hemorrhage was induced in rats by injecting 250 mu l of blood into the suprachiasmatic cistern, and gene regulation in the cerebral arteries was examined at various points in time following SAH by using quantitative polymerase chain reaction (PCR) and immunohistochemistry. Results. Immunohistochemical findings demonstrated that SAH phosphorylates and activates p38 and ERK1/2 as well as the downstream transcription factors Elk-1 and activating transcription factor-2. The pattern of activation consists of a rapid phase within the first few hours and a late phase that occurs from 24 to 48 hours. Activation is followed by an increase in the transcription of the inflammatory and ECM-related genes (IL6, TNF alpha, IL1 beta, CXCL1, CXCL2, CCL20, MMP8, MMP9, MMP13, and iNOS), as demonstrated using real-time PCR. For MMP13 and iNOS, the changes in transcription were translated into functional proteins, as revealed on immunohistochemistry. Conclusions. Activation of the p38 and ERK1/2 signaling pathways and their downstream transcription factors can explain the increase in the transcription of the genes studied. This increase and the subsequent augmentation in protein levels suggest that the inflammatory response may in part explain the remodeling that occurs in cerebral arteries following SAH. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1418104
- author
- Vikman, Petter LU ; Ansar, Saema LU and Edvinsson, Lars LU
- organization
- publishing date
- 2007
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- 5-HT1B RECEPTOR, UP-REGULATION, VASOSPASM, EXPRESSION, BRAIN, APOPTOSIS, CYTOKINES, MODELS, CELLS, BLOOD-FLOW, mitogen-activated protein kinase, extracellular matrix, inflammation, subarachnoid hemorrhage
- in
- Journal of Neurosurgery
- volume
- 107
- issue
- 5
- pages
- 1015 - 1022
- publisher
- American Association of Neurosurgeons
- external identifiers
-
- wos:000250878100017
- scopus:37149025398
- ISSN
- 0022-3085
- DOI
- 10.3171/jns-07/11/1015
- language
- English
- LU publication?
- yes
- id
- c7f4cd91-e749-4d04-9e51-9461249fd2f6 (old id 1418104)
- date added to LUP
- 2016-04-01 17:11:21
- date last changed
- 2024-01-11 22:18:10
@article{c7f4cd91-e749-4d04-9e51-9461249fd2f6,
abstract = {{Object. Subarachnoid hemorrhage (SAH) results in the expression of inflammatory and extracellular matrix (ECM)related genes and various G protein-coupled receptors. In the present study, the authors evaluated the time course and sequence of the transduction pathways, p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase-1 and 2 (ERK1/2), and associated transcription factor activation as well as gene regulation and associated protein levels. Methods. Subarachnoid hemorrhage was induced in rats by injecting 250 mu l of blood into the suprachiasmatic cistern, and gene regulation in the cerebral arteries was examined at various points in time following SAH by using quantitative polymerase chain reaction (PCR) and immunohistochemistry. Results. Immunohistochemical findings demonstrated that SAH phosphorylates and activates p38 and ERK1/2 as well as the downstream transcription factors Elk-1 and activating transcription factor-2. The pattern of activation consists of a rapid phase within the first few hours and a late phase that occurs from 24 to 48 hours. Activation is followed by an increase in the transcription of the inflammatory and ECM-related genes (IL6, TNF alpha, IL1 beta, CXCL1, CXCL2, CCL20, MMP8, MMP9, MMP13, and iNOS), as demonstrated using real-time PCR. For MMP13 and iNOS, the changes in transcription were translated into functional proteins, as revealed on immunohistochemistry. Conclusions. Activation of the p38 and ERK1/2 signaling pathways and their downstream transcription factors can explain the increase in the transcription of the genes studied. This increase and the subsequent augmentation in protein levels suggest that the inflammatory response may in part explain the remodeling that occurs in cerebral arteries following SAH.}},
author = {{Vikman, Petter and Ansar, Saema and Edvinsson, Lars}},
issn = {{0022-3085}},
keywords = {{5-HT1B RECEPTOR; UP-REGULATION; VASOSPASM; EXPRESSION; BRAIN; APOPTOSIS; CYTOKINES; MODELS; CELLS; BLOOD-FLOW; mitogen-activated protein kinase; extracellular matrix; inflammation; subarachnoid hemorrhage}},
language = {{eng}},
number = {{5}},
pages = {{1015--1022}},
publisher = {{American Association of Neurosurgeons}},
series = {{Journal of Neurosurgery}},
title = {{Transcriptional regulation of inflammatory and extracellular matrix-regulating genes in experimental subarachnoid cerebral arteries following hemorrhage in rats}},
url = {{http://dx.doi.org/10.3171/jns-07/11/1015}},
doi = {{10.3171/jns-07/11/1015}},
volume = {{107}},
year = {{2007}},
}