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.