These authors contributed equally to this work.
Role of stress-inducible protein-1 in recruitment of bone marrow derived cells into the ischemic brains
Article first published online: 8 JUL 2013
Copyright © 2013 EMBO Molecular Medicine
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
EMBO Molecular Medicine
Volume 5, Issue 8, pages 1227–1246, August 2013
How to Cite
Lee, S.-D., Lai, T. W., Lin, S.-Z., Lin, C.-H., Hsu, Y.-H., Li, C.-Y., Wang, H.-J., Lee, W., Su, C.-Y., Yu, Y.-L. and Shyu, W.-C. (2013), Role of stress-inducible protein-1 in recruitment of bone marrow derived cells into the ischemic brains. EMBO Mol Med, 5: 1227–1246. doi: 10.1002/emmm.201202258
- Issue published online: 5 AUG 2013
- Article first published online: 8 JUL 2013
- Manuscript Accepted: 17 MAY 2013
- Manuscript Revised: 15 MAY 2013
- Manuscript Received: 11 NOV 2012
- bone marrow derived cells (BMDCs);
- cell trafficking;
- hypoxia inducible factor 1α (HIF-1α);
- stress inducible protein type 1 (STI-1);
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.