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Periostin Promotes Neural Stem Cell Proliferation and Differentiation following Hypoxic-Ischemic Injury.

Ma SM, Chen LX, Lin YF, Yan H, Lv JW, Xiong M, Li J, Cheng GQ, Yang Y, Qiu ZL, Zhou WH - PLoS ONE (2015)

Bottom Line: Periostin (POSTN), a novel matricellular protein, plays pivotal roles in the survival, migration, and regeneration of various cell types, but its function in NSCs of neonatal rodent brain is still unknown.We found that POSTN mRNA levels significantly increased in differentiating NSCs.These results suggest that POSTN significantly enhances NSC proliferation and differentiation after HI, and provides new insights into therapeutic strategies for the treatment of hypoxic-ischemic encephalopathy.

View Article: PubMed Central - PubMed

Affiliation: Department of Neonatology, Children's Hospital of Fudan University, Shanghai, China; Key Laboratory of Neonatal Diseases, Ministry of Health, Children's Hospital of Fudan University, Shanghai, China.

ABSTRACT
Neural stem cell (NSC) proliferation and differentiation are required to replace neurons damaged or lost after hypoxic-ischemic events and recover brain function. Periostin (POSTN), a novel matricellular protein, plays pivotal roles in the survival, migration, and regeneration of various cell types, but its function in NSCs of neonatal rodent brain is still unknown. The purpose of this study was to investigate the role of POSTN in NSCs following hypoxia-ischemia (HI). We found that POSTN mRNA levels significantly increased in differentiating NSCs. The proliferation and differentiation of NSCs in the hippocampus is compromised in POSTN knockout mice. Moreover, NSC proliferation and differentiation into neurons and astrocytes significantly increased in cultured NSCs treated with recombinant POSTN. Consistently, injection of POSTN into neonatal hypoxic-ischemic rat brains stimulated NSC proliferation and differentiation in the subventricular and subgranular zones after 7 and 14 days of brain injury. Lastly, POSTN treatment significantly improved the spatial learning deficits of rats subjected to HI. These results suggest that POSTN significantly enhances NSC proliferation and differentiation after HI, and provides new insights into therapeutic strategies for the treatment of hypoxic-ischemic encephalopathy.

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Effects of POSTN on NSC proliferation and differentiation in the rat SVZ following HI.Hypoxic-ischemic injury (HI + PBS) stimulates NSC proliferation (A–C; BrdU+/Nestin+ cells) and differentiation into neurons (D–F; BrdU+/MAP2+ cells) and astrocytes (G–I; BrdU+/GFAP+ cells) at 7 and 14 days, but the effect is potentiated when POSTN is present (HI + POSTN). Cells were quantified per mm3 and data are shown as mean ± SEM. * or # P < 0.05; ** or ## P < 0.01; n = 8 animals per group. Scale bar = 100 μm.
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pone.0123585.g003: Effects of POSTN on NSC proliferation and differentiation in the rat SVZ following HI.Hypoxic-ischemic injury (HI + PBS) stimulates NSC proliferation (A–C; BrdU+/Nestin+ cells) and differentiation into neurons (D–F; BrdU+/MAP2+ cells) and astrocytes (G–I; BrdU+/GFAP+ cells) at 7 and 14 days, but the effect is potentiated when POSTN is present (HI + POSTN). Cells were quantified per mm3 and data are shown as mean ± SEM. * or # P < 0.05; ** or ## P < 0.01; n = 8 animals per group. Scale bar = 100 μm.

Mentions: Previous studies found that POSTN expression was increased in different tissues after injury [14–16]. Also, POSTN exhibited neuroprotective function in a transient middle cerebral artery occlusion model [20]. To examine the effects of POSTN on NSC proliferation and differentiation in vivo, recombinant POSTN was injected into the lateral ventricles of neonates following HI injury. Proliferating and differentiating NSCs were identified by combined immunodetection of BrdU and either Nestin, MAP2, or GFAP in the SVZ and SGZ. HI injury caused significant increases in the proliferation and differentiation of NSCs (HI+PBS) compared to animals that were not subjected to hypoxic-ischemic conditions (Sham+ PBS) (Fig 3 and 4). However, the number of BrdU+/Nestin+ cells in the SVZ was markedly increased after POSTN treatment (HI + POSTN) at 7 and 14 days (Fig 3A–3C). In contrast, treatment of POSTN in the absence of HI injury (Sham +POSTN) had no effect on NSC proliferation. Similar increases in BrdU+/MAP2+ (Fig 3D–3F) and BrdU+/GFAP+ (Fig 3G–3I) double-positive cells were observed after POSTN treatment, reflecting an increase in differentiation of NSCs into neurons and astrocytes, respectively. Consistent observations were also made for NSCs in the SGZ (Fig 4). The number of BrdU+/Nestin+ cells in the HI + POSTN group was significantly higher than those in HI + PBS-treated animals (Fig 4A–4C), demonstrating that NSC proliferation was stimulated by POSTN. The numbers of differentiated neurons (BrdU+/MAP2+ cells; Fig 4D–4F) and astrocytes (BrdU+/GFAP+ cells; Fig 4G–4I) were also higher in the HI + POSTN group at 7 and 14 days after HI compared to controls, consistent with a general effect of promoting differentiation rather than of specifying a particular cell type.


Periostin Promotes Neural Stem Cell Proliferation and Differentiation following Hypoxic-Ischemic Injury.

Ma SM, Chen LX, Lin YF, Yan H, Lv JW, Xiong M, Li J, Cheng GQ, Yang Y, Qiu ZL, Zhou WH - PLoS ONE (2015)

Effects of POSTN on NSC proliferation and differentiation in the rat SVZ following HI.Hypoxic-ischemic injury (HI + PBS) stimulates NSC proliferation (A–C; BrdU+/Nestin+ cells) and differentiation into neurons (D–F; BrdU+/MAP2+ cells) and astrocytes (G–I; BrdU+/GFAP+ cells) at 7 and 14 days, but the effect is potentiated when POSTN is present (HI + POSTN). Cells were quantified per mm3 and data are shown as mean ± SEM. * or # P < 0.05; ** or ## P < 0.01; n = 8 animals per group. Scale bar = 100 μm.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4404137&req=5

pone.0123585.g003: Effects of POSTN on NSC proliferation and differentiation in the rat SVZ following HI.Hypoxic-ischemic injury (HI + PBS) stimulates NSC proliferation (A–C; BrdU+/Nestin+ cells) and differentiation into neurons (D–F; BrdU+/MAP2+ cells) and astrocytes (G–I; BrdU+/GFAP+ cells) at 7 and 14 days, but the effect is potentiated when POSTN is present (HI + POSTN). Cells were quantified per mm3 and data are shown as mean ± SEM. * or # P < 0.05; ** or ## P < 0.01; n = 8 animals per group. Scale bar = 100 μm.
Mentions: Previous studies found that POSTN expression was increased in different tissues after injury [14–16]. Also, POSTN exhibited neuroprotective function in a transient middle cerebral artery occlusion model [20]. To examine the effects of POSTN on NSC proliferation and differentiation in vivo, recombinant POSTN was injected into the lateral ventricles of neonates following HI injury. Proliferating and differentiating NSCs were identified by combined immunodetection of BrdU and either Nestin, MAP2, or GFAP in the SVZ and SGZ. HI injury caused significant increases in the proliferation and differentiation of NSCs (HI+PBS) compared to animals that were not subjected to hypoxic-ischemic conditions (Sham+ PBS) (Fig 3 and 4). However, the number of BrdU+/Nestin+ cells in the SVZ was markedly increased after POSTN treatment (HI + POSTN) at 7 and 14 days (Fig 3A–3C). In contrast, treatment of POSTN in the absence of HI injury (Sham +POSTN) had no effect on NSC proliferation. Similar increases in BrdU+/MAP2+ (Fig 3D–3F) and BrdU+/GFAP+ (Fig 3G–3I) double-positive cells were observed after POSTN treatment, reflecting an increase in differentiation of NSCs into neurons and astrocytes, respectively. Consistent observations were also made for NSCs in the SGZ (Fig 4). The number of BrdU+/Nestin+ cells in the HI + POSTN group was significantly higher than those in HI + PBS-treated animals (Fig 4A–4C), demonstrating that NSC proliferation was stimulated by POSTN. The numbers of differentiated neurons (BrdU+/MAP2+ cells; Fig 4D–4F) and astrocytes (BrdU+/GFAP+ cells; Fig 4G–4I) were also higher in the HI + POSTN group at 7 and 14 days after HI compared to controls, consistent with a general effect of promoting differentiation rather than of specifying a particular cell type.

Bottom Line: Periostin (POSTN), a novel matricellular protein, plays pivotal roles in the survival, migration, and regeneration of various cell types, but its function in NSCs of neonatal rodent brain is still unknown.We found that POSTN mRNA levels significantly increased in differentiating NSCs.These results suggest that POSTN significantly enhances NSC proliferation and differentiation after HI, and provides new insights into therapeutic strategies for the treatment of hypoxic-ischemic encephalopathy.

View Article: PubMed Central - PubMed

Affiliation: Department of Neonatology, Children's Hospital of Fudan University, Shanghai, China; Key Laboratory of Neonatal Diseases, Ministry of Health, Children's Hospital of Fudan University, Shanghai, China.

ABSTRACT
Neural stem cell (NSC) proliferation and differentiation are required to replace neurons damaged or lost after hypoxic-ischemic events and recover brain function. Periostin (POSTN), a novel matricellular protein, plays pivotal roles in the survival, migration, and regeneration of various cell types, but its function in NSCs of neonatal rodent brain is still unknown. The purpose of this study was to investigate the role of POSTN in NSCs following hypoxia-ischemia (HI). We found that POSTN mRNA levels significantly increased in differentiating NSCs. The proliferation and differentiation of NSCs in the hippocampus is compromised in POSTN knockout mice. Moreover, NSC proliferation and differentiation into neurons and astrocytes significantly increased in cultured NSCs treated with recombinant POSTN. Consistently, injection of POSTN into neonatal hypoxic-ischemic rat brains stimulated NSC proliferation and differentiation in the subventricular and subgranular zones after 7 and 14 days of brain injury. Lastly, POSTN treatment significantly improved the spatial learning deficits of rats subjected to HI. These results suggest that POSTN significantly enhances NSC proliferation and differentiation after HI, and provides new insights into therapeutic strategies for the treatment of hypoxic-ischemic encephalopathy.

Show MeSH
Related in: MedlinePlus