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.

缺血性中风是世界范围内致残和死亡的主要原因。迫切需要一种有效的治疗方法。中风诱导的血管生成和神经发生是长期修复中必不可少的机制。细胞外基质蛋白也参与组织自我修复。最近，已鉴定出来自纤连蛋白协同基序的PHSRN（Pro-His-Ser-Arg-Asn）肽，该肽可促进上皮的伤口愈合并诱导内皮细胞增殖和癌细胞迁移。该肽在中风中的治疗潜力尚不清楚。在这里，我们使用缺血性大鼠大脑中动脉闭塞（MCAO）模型检查了PHSRN在中风治疗中的潜力。PHSRN减少了MCAO大鼠的梗塞体积，改善了神经功能，并减轻了运动功能障碍。腹腔注射后，PHSRN靶向受损的大脑区域并分布到内皮细胞。PHSRN通过激活整联蛋白α5β1及其下游细胞内信号（例如粘着斑激酶，Ras，cRaf和细胞外信号调节激酶），显着促进血管生成和血管内皮生长因子的分泌。PHSRN治疗还刺激MCAO大鼠的神经发生，并通过诱导VEGF分泌维持神经元存活和神经元形态复杂性。总之，这些结果提供了对整合素α5β1在缺血后的作用的见解，并支持在卒中治疗中使用PHSRN肽的可行性。PHSRN通过激活整联蛋白α5β1及其下游细胞内信号（例如粘着斑激酶，Ras，cRaf和细胞外信号调节激酶），显着促进血管生成和血管内皮生长因子的分泌。PHSRN治疗还刺激MCAO大鼠的神经发生，并通过诱导VEGF分泌维持神经元存活和神经元形态复杂性。总之，这些结果提供了对整合素α5β1在缺血后的作用的见解，并支持在卒中治疗中使用PHSRN肽的可行性。PHSRN通过激活整联蛋白α5β1及其下游细胞内信号（例如粘着斑激酶，Ras，cRaf和细胞外信号调节激酶），显着促进血管生成和血管内皮生长因子的分泌。PHSRN治疗还刺激MCAO大鼠的神经发生，并通过诱导VEGF分泌维持神经元存活和神经元形态复杂性。总之，这些结果提供了对整合素α5β1在缺血后的作用的见解，并支持在卒中治疗中使用PHSRN肽的可行性。并通过诱导VEGF分泌维持神经元存活和神经元形态复杂性。总之，这些结果提供了对整合素α5β1在缺血后的作用的见解，并支持在卒中治疗中使用PHSRN肽的可行性。并通过诱导VEGF分泌维持神经元存活和神经元形态复杂性。总之，这些结果提供了对整合素α5β1在缺血后的作用的见解，并支持在卒中治疗中使用PHSRN肽的可行性。