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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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Language:English
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0094695