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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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Expression of POSTN mRNA in cultured NSCs and the effect of POSTN deficiency on NSC proliferation and differentiation in SGZ.A: Compared to POSTN expression in proliferating NSCs (0 h), POSTN levels were increased at 48 h and 5 days following differentiation. B: POSTN is stably expressed in mouse neural stem cells. C: The protein expression of POSTN was decreased in the brain of POSTN+/- mice (KO) compared to wild-type mice (WT). D-E: The number of proliferating neurons was decreased at P7, 14, 21 and 28 in POSTN  mice. F-G: The number of proliferating NSCs was decreased in POSTN  mice at P7, 14, 21 and 28. Cells were quantified per mm3 and data are shown as mean ± SEM. * P < 0.05; ** P < 0.01; n = 9 animals per group. Scale bar = 50μm.
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pone.0123585.g001: Expression of POSTN mRNA in cultured NSCs and the effect of POSTN deficiency on NSC proliferation and differentiation in SGZ.A: Compared to POSTN expression in proliferating NSCs (0 h), POSTN levels were increased at 48 h and 5 days following differentiation. B: POSTN is stably expressed in mouse neural stem cells. C: The protein expression of POSTN was decreased in the brain of POSTN+/- mice (KO) compared to wild-type mice (WT). D-E: The number of proliferating neurons was decreased at P7, 14, 21 and 28 in POSTN mice. F-G: The number of proliferating NSCs was decreased in POSTN mice at P7, 14, 21 and 28. Cells were quantified per mm3 and data are shown as mean ± SEM. * P < 0.05; ** P < 0.01; n = 9 animals per group. Scale bar = 50μm.

Mentions: POSTN expression in mouse CNS spans from E12.5 to E19.5 [13]. To investigate the manner of POSTN expression during NSC differentiation, NSCs isolated from E12.5 mice were cultured in proliferation and differentiation media successively. The levels of POSTN gene expression at 0 h, 48 h and 5 days after differentiation were determined by quantitative real-time PCR. POSTN mRNA levels were significantly increased at 48 h and 5 days following NSC differentiation compared to proliferating NSCs (0 h) (Fig 1A). We also detected the POSTN protein expression in mouse NSCs. Western blot analysis showed that POSTN was stably expressed in mouse NSCs (Fig 1B).


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)

Expression of POSTN mRNA in cultured NSCs and the effect of POSTN deficiency on NSC proliferation and differentiation in SGZ.A: Compared to POSTN expression in proliferating NSCs (0 h), POSTN levels were increased at 48 h and 5 days following differentiation. B: POSTN is stably expressed in mouse neural stem cells. C: The protein expression of POSTN was decreased in the brain of POSTN+/- mice (KO) compared to wild-type mice (WT). D-E: The number of proliferating neurons was decreased at P7, 14, 21 and 28 in POSTN  mice. F-G: The number of proliferating NSCs was decreased in POSTN  mice at P7, 14, 21 and 28. Cells were quantified per mm3 and data are shown as mean ± SEM. * P < 0.05; ** P < 0.01; n = 9 animals per group. Scale bar = 50μm.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0123585.g001: Expression of POSTN mRNA in cultured NSCs and the effect of POSTN deficiency on NSC proliferation and differentiation in SGZ.A: Compared to POSTN expression in proliferating NSCs (0 h), POSTN levels were increased at 48 h and 5 days following differentiation. B: POSTN is stably expressed in mouse neural stem cells. C: The protein expression of POSTN was decreased in the brain of POSTN+/- mice (KO) compared to wild-type mice (WT). D-E: The number of proliferating neurons was decreased at P7, 14, 21 and 28 in POSTN mice. F-G: The number of proliferating NSCs was decreased in POSTN mice at P7, 14, 21 and 28. Cells were quantified per mm3 and data are shown as mean ± SEM. * P < 0.05; ** P < 0.01; n = 9 animals per group. Scale bar = 50μm.
Mentions: POSTN expression in mouse CNS spans from E12.5 to E19.5 [13]. To investigate the manner of POSTN expression during NSC differentiation, NSCs isolated from E12.5 mice were cultured in proliferation and differentiation media successively. The levels of POSTN gene expression at 0 h, 48 h and 5 days after differentiation were determined by quantitative real-time PCR. POSTN mRNA levels were significantly increased at 48 h and 5 days following NSC differentiation compared to proliferating NSCs (0 h) (Fig 1A). We also detected the POSTN protein expression in mouse NSCs. Western blot analysis showed that POSTN was stably expressed in mouse NSCs (Fig 1B).

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