Synthetic α5β1 integrin ligand PHSRN is proangiogenic and neuroprotective in cerebral ischemic stroke
| Autor: | Kuen Jer Tsai, Wei Yen Wei, Cheng Chun Wu, Yu Tin Su, Liang Chao Wang |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Vascular Endothelial Growth Factor A Angiogenesis Biophysics Ischemia Bioengineering Neuroprotection Brain Ischemia Biomaterials Focal adhesion Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals cardiovascular diseases Cells Cultured biology business.industry Neurogenesis Infarction Middle Cerebral Artery medicine.disease Peptide Fragments Fibronectins Fibronectin Vascular endothelial growth factor 030104 developmental biology Neuroprotective Agents chemistry Mechanics of Materials Ceramics and Composites biology.protein Cancer research Angiogenesis Inducing Agents business Wound healing 030217 neurology & neurosurgery Integrin alpha5beta1 Signal Transduction |
| Zdroj: | Biomaterials. 185 |
| ISSN: | 1878-5905 |
| Popis: | Ischemic stroke is the leading cause of disability and death worldwide. An effective therapeutic approach is urgently needed. Stroke-induced angiogenesis and neurogenesis are essential mechanisms in the long-term repair. Extracellular matrix proteins are also involved in tissue self-repair. Recently, a PHSRN (Pro-His-Ser-Arg-Asn) peptide from the fibronectin synergistic motif that can promote wound healing in epithelia and induce endothelial proliferation and cancer cell migration was identified. The therapeutic potential of this peptide in stroke is unknown. Here, we examined the potential of PHSRN in stroke therapy using an ischemic rat model of middle cerebral artery occlusion (MCAO). PHSRN reduced the infarct volume in MCAO rats, improved neurological function, and alleviated motor function impairment. PHSRN targeted the damaged brain region and distributed to endothelial cells after intraperitoneal injection. PHSRN significantly promoted angiogenesis and vascular endothelial growth factor secretion through activation of integrin α5β1 and its downstream intracellular signals, e.g., focal adhesion kinase, Ras, cRaf, and extracellular-signal-regulated kinase. PHSRN treatment also stimulated neurogenesis in MCAO rats, and maintained neuronal survival and neuronal morphologic complexity via induction of VEGF secretion. Together, these results provide insights into the role of integrin α5β1 following ischemia and support the feasibility of using PHSRN peptide in stroke therapy. |
| Databáze: | OpenAIRE |
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