Synthetic α5β1 integrin ligand PHSRN is proangiogenic and neuroprotective in cerebral ischemic stroke

Cheng Chun Wu, Liang-Chao Wang, Yu Tin Su, Wei Yen Wei, Kuen-Jer Tsai

研究成果: Article

2 引文 (Scopus)

摘要

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.

原文English
頁(從 - 到)142-154
頁數13
期刊Biomaterials
185
DOIs
出版狀態Published - 2018 十二月 1

指紋

prolyl-histidyl-seryl-arginyl-asparagine
Integrins
Peptides
Rats
Stroke
Ligands
Vascular Endothelial Growth Factor A
Repair
Middle Cerebral Artery Infarction
Focal Adhesion Protein-Tyrosine Kinases
Extracellular Matrix Proteins
Extracellular Signal-Regulated MAP Kinases
Endothelial cells
Fibronectins
Neurogenesis
Brain
Adhesion
Chemical activation
Cells
Tissue

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

引用此文

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title = "Synthetic α5β1 integrin ligand PHSRN is proangiogenic and neuroprotective in cerebral ischemic stroke",
abstract = "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.",
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Synthetic α5β1 integrin ligand PHSRN is proangiogenic and neuroprotective in cerebral ischemic stroke. / Wu, Cheng Chun; Wang, Liang-Chao; Su, Yu Tin; Wei, Wei Yen; Tsai, Kuen-Jer.

於: Biomaterials, 卷 185, 01.12.2018, p. 142-154.

研究成果: Article

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AU - Tsai, Kuen-Jer

PY - 2018/12/1

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N2 - 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.

AB - 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.

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