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AKAP12 mediates barrier functions of fibrotic scars during CNS repair

The repair process after CNS injury shows a well-organized cascade of three distinct stages: inflammation, new tissue formation, and remodeling. In the new tissue formation stage, various cells migrate and form the fibrotic scar surrounding the lesion site. The fibrotic scar is known as an obstacle...

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Published in:PloS one 2014-04, Vol.9 (4), p.e94695-e94695
Main Authors: Cha, Jong-Ho, Wee, Hee-Jun, Seo, Ji Hae, Ahn, Bum Ju, Park, Ji-Hyeon, Yang, Jun-Mo, Lee, Sae-Won, Kim, Eun Hee, Lee, Ok-Hee, Heo, Ji Hoe, Lee, Hyo-Jong, Gelman, Irwin H, Arai, Ken, Lo, Eng H, Kim, Kyu-Won
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cited_by cdi_FETCH-LOGICAL-c692t-98e7242c68c597b2f58a82a69c4fd413ddb26990be671bc4d0b211d109ece5fc3
cites cdi_FETCH-LOGICAL-c692t-98e7242c68c597b2f58a82a69c4fd413ddb26990be671bc4d0b211d109ece5fc3
container_end_page e94695
container_issue 4
container_start_page e94695
container_title PloS one
container_volume 9
creator Cha, Jong-Ho
Wee, Hee-Jun
Seo, Ji Hae
Ahn, Bum Ju
Park, Ji-Hyeon
Yang, Jun-Mo
Lee, Sae-Won
Kim, Eun Hee
Lee, Ok-Hee
Heo, Ji Hoe
Lee, Hyo-Jong
Gelman, Irwin H
Arai, Ken
Lo, Eng H
Kim, Kyu-Won
description The repair process after CNS injury shows a well-organized cascade of three distinct stages: inflammation, new tissue formation, and remodeling. In the new tissue formation stage, various cells migrate and form the fibrotic scar surrounding the lesion site. The fibrotic scar is known as an obstacle for axonal regeneration in the remodeling stage. However, the role of the fibrotic scar in the new tissue formation stage remains largely unknown. We found that the number of A-kinase anchoring protein 12 (AKAP12)-positive cells in the fibrotic scar was increased over time, and the cells formed a structure which traps various immune cells. Furthermore, the AKAP12-positive cells strongly express junction proteins which enable the structure to function as a physical barrier. In in vivo validation, AKAP12 knock-out (KO) mice showed leakage from a lesion, resulting from an impaired structure with the loss of the junction complex. Consistently, focal brain injury in the AKAP12 KO mice led to extended inflammation and more severe tissue damage compared to the wild type (WT) mice. Accordingly, our results suggest that AKAP12-positive cells in the fibrotic scar may restrict excessive inflammation, demonstrating certain mechanisms that could underlie the beneficial actions of the fibrotic scar in the new tissue formation stage during the CNS repair process.
doi_str_mv 10.1371/journal.pone.0094695
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In the new tissue formation stage, various cells migrate and form the fibrotic scar surrounding the lesion site. The fibrotic scar is known as an obstacle for axonal regeneration in the remodeling stage. However, the role of the fibrotic scar in the new tissue formation stage remains largely unknown. We found that the number of A-kinase anchoring protein 12 (AKAP12)-positive cells in the fibrotic scar was increased over time, and the cells formed a structure which traps various immune cells. Furthermore, the AKAP12-positive cells strongly express junction proteins which enable the structure to function as a physical barrier. In in vivo validation, AKAP12 knock-out (KO) mice showed leakage from a lesion, resulting from an impaired structure with the loss of the junction complex. Consistently, focal brain injury in the AKAP12 KO mice led to extended inflammation and more severe tissue damage compared to the wild type (WT) mice. 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subjects A Kinase Anchor Proteins - genetics
A Kinase Anchor Proteins - metabolism
A kinase-anchoring protein
Anchoring
Animals
Biology and Life Sciences
Blood-brain barrier
Blotting, Western
Brain
Brain injury
Brain research
Cancer
Cardiovascular disease
Cell Cycle Proteins - genetics
Cell Cycle Proteins - metabolism
Cell migration
Central nervous system
Central Nervous System - metabolism
Departments
Fibrosis
Fibrosis - genetics
Fibrosis - metabolism
Genetic aspects
Head injuries
Hospitals
Hypoxia
Immune system
Injuries
Laboratories
Male
Medicine
Medicine and Health Sciences
Mice
Mice, Inbred C57BL
Mice, Knockout
Motility
Nervous system
Neurology
Pharmaceutical sciences
Pharmacy
Physiological aspects
Protein kinases
Proteins
Rats, Wistar
Regeneration
Repair
Research and Analysis Methods
Rodents
Scars
Spinal cord injuries
Stem cells
Structure-function relationships
Studies
Wound Healing - genetics
Wound Healing - physiology
title AKAP12 mediates barrier functions of fibrotic scars during CNS repair
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