Limits...
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.

Show MeSH

Related in: MedlinePlus

Effects of POSTN on NSC proliferation and differentiation in vitro.A–C: The presence of POSTN (+POSTN) increases the number of proliferating NSCs at 5 and 7 days after plating, as evidenced by an increase in BrdU+/Nestin+ double-positive cells. D–F: The fraction of NSCs undergoing differentiation into neurons (BrdU+/MAP2+ cells) increases at 7 days after plating when POSTN is present. G–I: The fraction of NSCs undergoing differentiation into astrocytes (BrdU+/GFAP+ cells) increased at 7 days after plating in the presence of POSTN. The ratio of double-positive cells to the total number of cells is shown as mean ± SEM (* P < 0.05 from three independent experiments). Scale bar = 100 μm.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4404137&req=5

pone.0123585.g002: Effects of POSTN on NSC proliferation and differentiation in vitro.A–C: The presence of POSTN (+POSTN) increases the number of proliferating NSCs at 5 and 7 days after plating, as evidenced by an increase in BrdU+/Nestin+ double-positive cells. D–F: The fraction of NSCs undergoing differentiation into neurons (BrdU+/MAP2+ cells) increases at 7 days after plating when POSTN is present. G–I: The fraction of NSCs undergoing differentiation into astrocytes (BrdU+/GFAP+ cells) increased at 7 days after plating in the presence of POSTN. The ratio of double-positive cells to the total number of cells is shown as mean ± SEM (* P < 0.05 from three independent experiments). Scale bar = 100 μm.

Mentions: To investigate the effects of POSTN on NSC proliferation and differentiation in vitro, NSCs were cultured in the presence of 50 ng/mL POSTN. Proliferating NSCs were identified as cells double-positive for BrdU and Nestin (BrdU+/Nestin+), while BrdU+/MAP2+ and BrdU+/GFAP+ cells represented NSCs differentiating into neurons and astrocytes, respectively. NSCs cultured in the presence of POSTN showed a prominent enhancement in proliferation (Fig 2A and 2B). Proliferation rates were significantly increased at 5 and 7 days after NSC differentiation compared to control NSCs (Fig 2C). Similarly, the numbers of neurons (Fig 2D–2F) and astrocytes (Fig 2G–2I) were increased after POSTN treatment compared to controls, although these increases were not statistically significant until 7 days after differentiation.


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 vitro.A–C: The presence of POSTN (+POSTN) increases the number of proliferating NSCs at 5 and 7 days after plating, as evidenced by an increase in BrdU+/Nestin+ double-positive cells. D–F: The fraction of NSCs undergoing differentiation into neurons (BrdU+/MAP2+ cells) increases at 7 days after plating when POSTN is present. G–I: The fraction of NSCs undergoing differentiation into astrocytes (BrdU+/GFAP+ cells) increased at 7 days after plating in the presence of POSTN. The ratio of double-positive cells to the total number of cells is shown as mean ± SEM (* P < 0.05 from three independent experiments). Scale bar = 100 μm.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0123585.g002: Effects of POSTN on NSC proliferation and differentiation in vitro.A–C: The presence of POSTN (+POSTN) increases the number of proliferating NSCs at 5 and 7 days after plating, as evidenced by an increase in BrdU+/Nestin+ double-positive cells. D–F: The fraction of NSCs undergoing differentiation into neurons (BrdU+/MAP2+ cells) increases at 7 days after plating when POSTN is present. G–I: The fraction of NSCs undergoing differentiation into astrocytes (BrdU+/GFAP+ cells) increased at 7 days after plating in the presence of POSTN. The ratio of double-positive cells to the total number of cells is shown as mean ± SEM (* P < 0.05 from three independent experiments). Scale bar = 100 μm.
Mentions: To investigate the effects of POSTN on NSC proliferation and differentiation in vitro, NSCs were cultured in the presence of 50 ng/mL POSTN. Proliferating NSCs were identified as cells double-positive for BrdU and Nestin (BrdU+/Nestin+), while BrdU+/MAP2+ and BrdU+/GFAP+ cells represented NSCs differentiating into neurons and astrocytes, respectively. NSCs cultured in the presence of POSTN showed a prominent enhancement in proliferation (Fig 2A and 2B). Proliferation rates were significantly increased at 5 and 7 days after NSC differentiation compared to control NSCs (Fig 2C). Similarly, the numbers of neurons (Fig 2D–2F) and astrocytes (Fig 2G–2I) were increased after POSTN treatment compared to controls, although these increases were not statistically significant until 7 days after differentiation.

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