Lack of collagen XV is protective after ischemic stroke in mice
|Author:||Dhungana, Hiramani1; Huuskonen, Mikko T1; Pihlajaniemi, Taina2;|
1Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland
2Oulu Center for Cell-Matrix Research, Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
3Centre for Cancer Biomarkers CCBIO, Department of Biomedicine, University of Bergen, Bergen, Norway
4Normandie Univ, UNICAEN, INSERM U919, Serine Proteases and Pathophysiology of the neurovascular Unit, Cyceron, Caen, France
5Department of Clinical Research, Caen University Hospital, Avenue de la côte de Nacre, Caen, France
|Online Access:||PDF Full Text (PDF, 1.7 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe201704116051
Nature Publishing Group,
|Publish Date:|| 2017-04-11
Collagens are key structural components of basement membranes, providing a scaffold for other components or adhering cells. Collagens and collagen-derived active fragments contribute to biological activities such as cell growth, differentiation and migration. Here, we report that collagen XV knock-out (ColXV KO) mice are resistant to experimental ischemic stroke. Interestingly, the infarcts of ColXV KO mice were as small as those of wild-type (WT) mice thrombolysed with recombinant tissue plasminogen activator (rtPA), the actual treatment for ischemic stroke. Importantly, there were no differences in the architecture of cerebrovascular anatomy between WT and ColXV KO mice. We found a twofold increase of the most potent pro-angiogenic factor, type A vascular growth endothelial factor (VEGF-A) in the ipsilateral cortex of rtPA-treated ischemic WT mice compared with untreated ischemic and sham-operated counterparts. A similar increase of VEGF-A was also found in both rtPA and untreated ischemic ColXV KO mice compared with sham ColXV KO mice. Finally, we evidenced that the levels of ColXV were increased in the plasma of WT mice treated with rtPA compared with untreated ischemic counterparts. Altogether, this study indicates that the lack ColXV is protective after stroke and that the degradation of endothelial ColXV may contribute to the beneficial effect of rtPA after ischemic stroke. The neuroprotection observed in ColXV KO mice may be attributed to the increased VEGF-A production following stroke in the ischemic territory.
Cell death and disease
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
1182 Biochemistry, cell and molecular biology
This work was supported by the Council for Health Sciences and the Centre of Excellence Program 2012–2017 of the Academy of Finland (Grant 251314), the INSERM, the ERANET-Neuron research program ‘ProteA: Proteases before, during and after stroke’, 2012–2015, and the Sigrid Jusélius Foundation.
|Academy of Finland Grant Number:||
251314 (Academy of Finland Funding decision)
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