Leucine Zipper-Bearing Kinase Is a Critical Regulator of Astrocyte Reactivity in the Adult Mammalian CNS
Summary: Reactive astrocytes influence post-injury recovery, repair, and pathogenesis of the mammalian CNS. Much of the regulation of astrocyte reactivity, however, remains to be understood. Using genetic loss and gain-of-function analyses in vivo, we show that the conserved MAP3K13 (also known as l...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2018-03-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718303127 |
| _version_ | 1811226240632225792 |
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| author | Meifan Chen Cédric G. Geoffroy Jessica M. Meves Aarti Narang Yunbo Li Mallorie T. Nguyen Vung S. Khai Xiangmei Kong Christopher L. Steinke Krislyn I. Carolino Lucie Elzière Mark P. Goldberg Yishi Jin Binhai Zheng |
| author_facet | Meifan Chen Cédric G. Geoffroy Jessica M. Meves Aarti Narang Yunbo Li Mallorie T. Nguyen Vung S. Khai Xiangmei Kong Christopher L. Steinke Krislyn I. Carolino Lucie Elzière Mark P. Goldberg Yishi Jin Binhai Zheng |
| author_sort | Meifan Chen |
| collection | DOAJ |
| description | Summary: Reactive astrocytes influence post-injury recovery, repair, and pathogenesis of the mammalian CNS. Much of the regulation of astrocyte reactivity, however, remains to be understood. Using genetic loss and gain-of-function analyses in vivo, we show that the conserved MAP3K13 (also known as leucine zipper-bearing kinase [LZK]) promotes astrocyte reactivity and glial scar formation after CNS injury. Inducible LZK gene deletion in astrocytes of adult mice reduced astrogliosis and impaired glial scar formation, resulting in increased lesion size after spinal cord injury. Conversely, LZK overexpression in astrocytes enhanced astrogliosis and reduced lesion size. Remarkably, in the absence of injury, LZK overexpression alone induced widespread astrogliosis in the CNS and upregulated astrogliosis activators pSTAT3 and SOX9. The identification of LZK as a critical cell-intrinsic regulator of astrocyte reactivity expands our understanding of the multicellular response to CNS injury and disease, with broad translational implications for neural repair. : Reactive astrocytes are recognized increasingly for their role in CNS injury and disease. Chen et al. find that leucine zipper-bearing kinase (LZK) is a positive regulator of astrocyte reactivity that controls glial scar formation after spinal cord injury. These findings have broad implications for understanding injury responses and promoting neural repair. Keywords: CNS injury, spinal cord injury, astrogliosis, glial scar, astroglial reactivity, reactive astrocytes, LZK, MAP3K, SOX9, STAT3 |
| first_indexed | 2024-04-12T09:21:42Z |
| format | Article |
| id | doaj.art-899c443c4e10416bbd9bcf35dc2f9502 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-12T09:21:42Z |
| publishDate | 2018-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-899c443c4e10416bbd9bcf35dc2f95022022-12-22T03:38:38ZengElsevierCell Reports2211-12472018-03-01221335873597Leucine Zipper-Bearing Kinase Is a Critical Regulator of Astrocyte Reactivity in the Adult Mammalian CNSMeifan Chen0Cédric G. Geoffroy1Jessica M. Meves2Aarti Narang3Yunbo Li4Mallorie T. Nguyen5Vung S. Khai6Xiangmei Kong7Christopher L. Steinke8Krislyn I. Carolino9Lucie Elzière10Mark P. Goldberg11Yishi Jin12Binhai Zheng13Department of Neurosciences, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA; Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USADepartment of Neurosciences, School of Medicine, University of California San Diego, La Jolla, CA 92093, USADepartment of Neurosciences, School of Medicine, University of California San Diego, La Jolla, CA 92093, USADepartment of Neurosciences, School of Medicine, University of California San Diego, La Jolla, CA 92093, USASection of Neurobiology, Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093, USADepartment of Neurosciences, School of Medicine, University of California San Diego, La Jolla, CA 92093, USADepartment of Neurosciences, School of Medicine, University of California San Diego, La Jolla, CA 92093, USADepartment of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USASection of Neurobiology, Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093, USADepartment of Neurosciences, School of Medicine, University of California San Diego, La Jolla, CA 92093, USADepartment of Neurosciences, School of Medicine, University of California San Diego, La Jolla, CA 92093, USADepartment of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Corresponding authorDepartment of Neurosciences, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA; Section of Neurobiology, Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093, USA; Corresponding authorDepartment of Neurosciences, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA; Corresponding authorSummary: Reactive astrocytes influence post-injury recovery, repair, and pathogenesis of the mammalian CNS. Much of the regulation of astrocyte reactivity, however, remains to be understood. Using genetic loss and gain-of-function analyses in vivo, we show that the conserved MAP3K13 (also known as leucine zipper-bearing kinase [LZK]) promotes astrocyte reactivity and glial scar formation after CNS injury. Inducible LZK gene deletion in astrocytes of adult mice reduced astrogliosis and impaired glial scar formation, resulting in increased lesion size after spinal cord injury. Conversely, LZK overexpression in astrocytes enhanced astrogliosis and reduced lesion size. Remarkably, in the absence of injury, LZK overexpression alone induced widespread astrogliosis in the CNS and upregulated astrogliosis activators pSTAT3 and SOX9. The identification of LZK as a critical cell-intrinsic regulator of astrocyte reactivity expands our understanding of the multicellular response to CNS injury and disease, with broad translational implications for neural repair. : Reactive astrocytes are recognized increasingly for their role in CNS injury and disease. Chen et al. find that leucine zipper-bearing kinase (LZK) is a positive regulator of astrocyte reactivity that controls glial scar formation after spinal cord injury. These findings have broad implications for understanding injury responses and promoting neural repair. Keywords: CNS injury, spinal cord injury, astrogliosis, glial scar, astroglial reactivity, reactive astrocytes, LZK, MAP3K, SOX9, STAT3http://www.sciencedirect.com/science/article/pii/S2211124718303127 |
| spellingShingle | Meifan Chen Cédric G. Geoffroy Jessica M. Meves Aarti Narang Yunbo Li Mallorie T. Nguyen Vung S. Khai Xiangmei Kong Christopher L. Steinke Krislyn I. Carolino Lucie Elzière Mark P. Goldberg Yishi Jin Binhai Zheng Leucine Zipper-Bearing Kinase Is a Critical Regulator of Astrocyte Reactivity in the Adult Mammalian CNS Cell Reports |
| title | Leucine Zipper-Bearing Kinase Is a Critical Regulator of Astrocyte Reactivity in the Adult Mammalian CNS |
| title_full | Leucine Zipper-Bearing Kinase Is a Critical Regulator of Astrocyte Reactivity in the Adult Mammalian CNS |
| title_fullStr | Leucine Zipper-Bearing Kinase Is a Critical Regulator of Astrocyte Reactivity in the Adult Mammalian CNS |
| title_full_unstemmed | Leucine Zipper-Bearing Kinase Is a Critical Regulator of Astrocyte Reactivity in the Adult Mammalian CNS |
| title_short | Leucine Zipper-Bearing Kinase Is a Critical Regulator of Astrocyte Reactivity in the Adult Mammalian CNS |
| title_sort | leucine zipper bearing kinase is a critical regulator of astrocyte reactivity in the adult mammalian cns |
| url | http://www.sciencedirect.com/science/article/pii/S2211124718303127 |
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