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...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0094695&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850026624403111936 |
|---|---|
| author | Jong-Ho Cha Hee-Jun Wee Ji Hae Seo Bum Ju Ahn Ji-Hyeon Park Jun-Mo Yang Sae-Won Lee Eun Hee Kim Ok-Hee Lee Ji Hoe Heo Hyo-Jong Lee Irwin H Gelman Ken Arai Eng H Lo Kyu-Won Kim |
| author_facet | Jong-Ho Cha Hee-Jun Wee Ji Hae Seo Bum Ju Ahn Ji-Hyeon Park Jun-Mo Yang Sae-Won Lee Eun Hee Kim Ok-Hee Lee Ji Hoe Heo Hyo-Jong Lee Irwin H Gelman Ken Arai Eng H Lo Kyu-Won Kim |
| author_sort | Jong-Ho Cha |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-3d669d77a7bf4175a36a6ae26c8739f9 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-3d669d77a7bf4175a36a6ae26c8739f92025-08-20T03:00:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9469510.1371/journal.pone.0094695AKAP12 mediates barrier functions of fibrotic scars during CNS repair.Jong-Ho ChaHee-Jun WeeJi Hae SeoBum Ju AhnJi-Hyeon ParkJun-Mo YangSae-Won LeeEun Hee KimOk-Hee LeeJi Hoe HeoHyo-Jong LeeIrwin H GelmanKen AraiEng H LoKyu-Won KimThe 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0094695&type=printable |
| spellingShingle | Jong-Ho Cha Hee-Jun Wee Ji Hae Seo Bum Ju Ahn Ji-Hyeon Park Jun-Mo Yang Sae-Won Lee Eun Hee Kim Ok-Hee Lee Ji Hoe Heo Hyo-Jong Lee Irwin H Gelman Ken Arai Eng H Lo Kyu-Won Kim AKAP12 mediates barrier functions of fibrotic scars during CNS repair. PLoS ONE |
| title | AKAP12 mediates barrier functions of fibrotic scars during CNS repair. |
| title_full | AKAP12 mediates barrier functions of fibrotic scars during CNS repair. |
| title_fullStr | AKAP12 mediates barrier functions of fibrotic scars during CNS repair. |
| title_full_unstemmed | AKAP12 mediates barrier functions of fibrotic scars during CNS repair. |
| title_short | AKAP12 mediates barrier functions of fibrotic scars during CNS repair. |
| title_sort | akap12 mediates barrier functions of fibrotic scars during cns repair |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0094695&type=printable |
| work_keys_str_mv | AT jonghocha akap12mediatesbarrierfunctionsoffibroticscarsduringcnsrepair AT heejunwee akap12mediatesbarrierfunctionsoffibroticscarsduringcnsrepair AT jihaeseo akap12mediatesbarrierfunctionsoffibroticscarsduringcnsrepair AT bumjuahn akap12mediatesbarrierfunctionsoffibroticscarsduringcnsrepair AT jihyeonpark akap12mediatesbarrierfunctionsoffibroticscarsduringcnsrepair AT junmoyang akap12mediatesbarrierfunctionsoffibroticscarsduringcnsrepair AT saewonlee akap12mediatesbarrierfunctionsoffibroticscarsduringcnsrepair AT eunheekim akap12mediatesbarrierfunctionsoffibroticscarsduringcnsrepair AT okheelee akap12mediatesbarrierfunctionsoffibroticscarsduringcnsrepair AT jihoeheo akap12mediatesbarrierfunctionsoffibroticscarsduringcnsrepair AT hyojonglee akap12mediatesbarrierfunctionsoffibroticscarsduringcnsrepair AT irwinhgelman akap12mediatesbarrierfunctionsoffibroticscarsduringcnsrepair AT kenarai akap12mediatesbarrierfunctionsoffibroticscarsduringcnsrepair AT enghlo akap12mediatesbarrierfunctionsoffibroticscarsduringcnsrepair AT kyuwonkim akap12mediatesbarrierfunctionsoffibroticscarsduringcnsrepair |