Role of stress‐inducible protein‐1 in recruitment of bone marrow derived cells into the ischemic brains
Abstract Stress‐inducible protein‐1 (STI‐1) is the proposed ligand for the cellular prion protein (PrPC), which is thought to facilitate recovery following stroke. Whether STI‐1 expression is affected by stroke and how its signalling facilitates recovery remain elusive. Brain slices from patients th...
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| Format: | Article |
| Language: | English |
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Springer Nature
2013-07-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.1002/emmm.201202258 |
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| author | Shin‐Da Lee Ted Weita Lai Shinn‐Zong Lin Chen‐Huan Lin Yung‐Hsiang Hsu Chi‐Yuan Li Hsiao‐Jung Wang Wei Lee Ching‐Yuan Su Yung‐Luen Yu Woei‐Cherng Shyu |
| author_facet | Shin‐Da Lee Ted Weita Lai Shinn‐Zong Lin Chen‐Huan Lin Yung‐Hsiang Hsu Chi‐Yuan Li Hsiao‐Jung Wang Wei Lee Ching‐Yuan Su Yung‐Luen Yu Woei‐Cherng Shyu |
| author_sort | Shin‐Da Lee |
| collection | DOAJ |
| description | Abstract Stress‐inducible protein‐1 (STI‐1) is the proposed ligand for the cellular prion protein (PrPC), which is thought to facilitate recovery following stroke. Whether STI‐1 expression is affected by stroke and how its signalling facilitates recovery remain elusive. Brain slices from patients that died of ischemic stroke were collected for STI‐1 immunohistochemistry. These findings were compared to results from cell cultures, mice with or without the PrPC knockout, and rats. Based on these findings, molecular and pharmacological interventions were administered to investigate the underlying mechanisms and to test the possibility for therapy in experimental stroke models. STI‐1 was upregulated in the ischemic brains from humans and rodents. The increase in STI‐1 expression in vivo was not cell‐type specific, as it was found in neurons, glia and endothelial cells. Likewise, this increase in STI‐1 expression can be mimicked by sublethal hypoxia in primary cortical cultures (PCCs) in vitro, and appear to have resulted from the direct binding of the hypoxia inducible factor‐1α (HIF‐1α) to the STI‐1 promoter. Importantly, this STI‐1 signalling promoted bone marrow derived cells (BMDCs) proliferation and migration in vitro and recruitment to the ischemic brain in vivo, and augmenting its signalling facilitated neurological recovery in part by recruiting BMDCs to the ischemic brain. Our results thus identified a novel mechanism by which ischemic insults can trigger a self‐protective mechanism to facilitate recovery. |
| format | Article |
| id | doaj-art-aa4bc6ab336c42e7a40212e92d7ab28e |
| institution | OA Journals |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2013-07-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-aa4bc6ab336c42e7a40212e92d7ab28e2025-08-20T02:11:26ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842013-07-01581227124610.1002/emmm.201202258Role of stress‐inducible protein‐1 in recruitment of bone marrow derived cells into the ischemic brainsShin‐Da Lee0Ted Weita Lai1Shinn‐Zong Lin2Chen‐Huan Lin3Yung‐Hsiang Hsu4Chi‐Yuan Li5Hsiao‐Jung Wang6Wei Lee7Ching‐Yuan Su8Yung‐Luen Yu9Woei‐Cherng Shyu10Department of Physical Therapy, Graduate Institute of Rehabilitation Science, China Medical UniversityGraduate Institute of Clinical Medical Science, China Medical UniversityGraduate Institute of Immunology, China Medical UniversityCenter for Neuropsychiatry, Department of Neurology, China Medical University HospitalDepartment of Pathology, Buddhist Tzu‐Chi General Hospital, Tzu‐Chi UniversityGraduate Institute of Clinical Medical Science, China Medical UniversityTranslational Medicine Research Center, China Medical University HospitalTranslational Medicine Research Center, China Medical University HospitalInstitute of Molecular Biology, Academia SinicaGraduate Institute of Cancer Biology, Center for Molecular Medicine, China Medical UniversityTranslational Medicine Research Center, China Medical University HospitalAbstract Stress‐inducible protein‐1 (STI‐1) is the proposed ligand for the cellular prion protein (PrPC), which is thought to facilitate recovery following stroke. Whether STI‐1 expression is affected by stroke and how its signalling facilitates recovery remain elusive. Brain slices from patients that died of ischemic stroke were collected for STI‐1 immunohistochemistry. These findings were compared to results from cell cultures, mice with or without the PrPC knockout, and rats. Based on these findings, molecular and pharmacological interventions were administered to investigate the underlying mechanisms and to test the possibility for therapy in experimental stroke models. STI‐1 was upregulated in the ischemic brains from humans and rodents. The increase in STI‐1 expression in vivo was not cell‐type specific, as it was found in neurons, glia and endothelial cells. Likewise, this increase in STI‐1 expression can be mimicked by sublethal hypoxia in primary cortical cultures (PCCs) in vitro, and appear to have resulted from the direct binding of the hypoxia inducible factor‐1α (HIF‐1α) to the STI‐1 promoter. Importantly, this STI‐1 signalling promoted bone marrow derived cells (BMDCs) proliferation and migration in vitro and recruitment to the ischemic brain in vivo, and augmenting its signalling facilitated neurological recovery in part by recruiting BMDCs to the ischemic brain. Our results thus identified a novel mechanism by which ischemic insults can trigger a self‐protective mechanism to facilitate recovery.https://doi.org/10.1002/emmm.201202258bone marrow derived cells (BMDCs)cell traffickinghypoxia inducible factor 1α (HIF‐1α)stress inducible protein type 1 (STI‐1)stroke |
| spellingShingle | Shin‐Da Lee Ted Weita Lai Shinn‐Zong Lin Chen‐Huan Lin Yung‐Hsiang Hsu Chi‐Yuan Li Hsiao‐Jung Wang Wei Lee Ching‐Yuan Su Yung‐Luen Yu Woei‐Cherng Shyu Role of stress‐inducible protein‐1 in recruitment of bone marrow derived cells into the ischemic brains EMBO Molecular Medicine bone marrow derived cells (BMDCs) cell trafficking hypoxia inducible factor 1α (HIF‐1α) stress inducible protein type 1 (STI‐1) stroke |
| title | Role of stress‐inducible protein‐1 in recruitment of bone marrow derived cells into the ischemic brains |
| title_full | Role of stress‐inducible protein‐1 in recruitment of bone marrow derived cells into the ischemic brains |
| title_fullStr | Role of stress‐inducible protein‐1 in recruitment of bone marrow derived cells into the ischemic brains |
| title_full_unstemmed | Role of stress‐inducible protein‐1 in recruitment of bone marrow derived cells into the ischemic brains |
| title_short | Role of stress‐inducible protein‐1 in recruitment of bone marrow derived cells into the ischemic brains |
| title_sort | role of stress inducible protein 1 in recruitment of bone marrow derived cells into the ischemic brains |
| topic | bone marrow derived cells (BMDCs) cell trafficking hypoxia inducible factor 1α (HIF‐1α) stress inducible protein type 1 (STI‐1) stroke |
| url | https://doi.org/10.1002/emmm.201202258 |
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