PEDF promotes the repair of bone marrow endothelial cell injury and accelerates hematopoietic reconstruction after bone marrow transplantation.


Journal

Journal of biomedical science
ISSN: 1423-0127
Titre abrégé: J Biomed Sci
Pays: England
ID NLM: 9421567

Informations de publication

Date de publication:
01 Sep 2020
Historique:
received: 19 02 2020
accepted: 26 08 2020
entrez: 3 9 2020
pubmed: 3 9 2020
medline: 26 5 2021
Statut: epublish

Résumé

Preconditioning before bone marrow transplantation such as irradiation causes vascular endothelial cells damage and promoting the repair of damaged endothelial cells is beneficial for hematopoietic reconstitution. Pigment epithelium-derived factor (PEDF) regulates vascular permeability. However, PEDF's role in the repair of damaged endothelial cells during preconditioning remains unclear. The purpose of our study is to investigate PEDF's effect on preconditioning-induced damage of endothelial cells and hematopoietic reconstitution. Damaged endothelial cells induced by irradiation was co-cultured with hematopoietic stem cells (HSC) in the absence or presence of PEDF followed by analysis of HSC number, cell cycle, colony formation and differentiation. In addition, PEDF was injected into mice model of bone marrow transplantation followed by analysis of bone marrow injury, HSC number and peripheral hematopoietic reconstitution as well as the secretion of cytokines (SCF, TGF-β, IL-6 and TNF-α). Comparisons between two groups were performed by student t-test and multiple groups by one-way or two-way ANOVA. Damaged endothelial cells reduced HSC expansion and colony formation, induced HSC cell cycle arrest and apoptosis and promoted HSC differentiation as well as decreased PEDF expression. Addition of PEDF increased CD144 expression in damaged endothelial cells and inhibited the increase of endothelial permeability, which were abolished after addition of PEDF receptor inhibitor Atglistatin. Additionally, PEDF ameliorated the inhibitory effect of damaged endothelial cells on HSC expansion in vitro. Finally, PEDF accelerated hematopoietic reconstitution after bone marrow transplantation in mice and promoted the secretion of SCF, TGF-β and IL-6. PEDF inhibits the increased endothelial permeability induced by irradiation and reverse the inhibitory effect of injured endothelial cells on hematopoietic stem cells and promote hematopoietic reconstruction.

Sections du résumé

BACKGROUND BACKGROUND
Preconditioning before bone marrow transplantation such as irradiation causes vascular endothelial cells damage and promoting the repair of damaged endothelial cells is beneficial for hematopoietic reconstitution. Pigment epithelium-derived factor (PEDF) regulates vascular permeability. However, PEDF's role in the repair of damaged endothelial cells during preconditioning remains unclear. The purpose of our study is to investigate PEDF's effect on preconditioning-induced damage of endothelial cells and hematopoietic reconstitution.
METHODS METHODS
Damaged endothelial cells induced by irradiation was co-cultured with hematopoietic stem cells (HSC) in the absence or presence of PEDF followed by analysis of HSC number, cell cycle, colony formation and differentiation. In addition, PEDF was injected into mice model of bone marrow transplantation followed by analysis of bone marrow injury, HSC number and peripheral hematopoietic reconstitution as well as the secretion of cytokines (SCF, TGF-β, IL-6 and TNF-α). Comparisons between two groups were performed by student t-test and multiple groups by one-way or two-way ANOVA.
RESULTS RESULTS
Damaged endothelial cells reduced HSC expansion and colony formation, induced HSC cell cycle arrest and apoptosis and promoted HSC differentiation as well as decreased PEDF expression. Addition of PEDF increased CD144 expression in damaged endothelial cells and inhibited the increase of endothelial permeability, which were abolished after addition of PEDF receptor inhibitor Atglistatin. Additionally, PEDF ameliorated the inhibitory effect of damaged endothelial cells on HSC expansion in vitro. Finally, PEDF accelerated hematopoietic reconstitution after bone marrow transplantation in mice and promoted the secretion of SCF, TGF-β and IL-6.
CONCLUSIONS CONCLUSIONS
PEDF inhibits the increased endothelial permeability induced by irradiation and reverse the inhibitory effect of injured endothelial cells on hematopoietic stem cells and promote hematopoietic reconstruction.

Identifiants

pubmed: 32873283
doi: 10.1186/s12929-020-00685-4
pii: 10.1186/s12929-020-00685-4
pmc: PMC7466818
doi:

Substances chimiques

Eye Proteins 0
Nerve Growth Factors 0
Serpins 0
pigment epithelium-derived factor 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

91

Subventions

Organisme : National Natural Science Foundation of China (CN)
ID : 31872795

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Auteurs

Wen Ju (W)

Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China.
Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China.
Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.

Wenyi Lu (W)

Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China.
Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China.
Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.

Lan Ding (L)

Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China.
Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China.
Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.

Yurong Bao (Y)

Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China.
Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China.
Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.

Fei Hong (F)

Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China.
Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China.
Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.

Yuting Chen (Y)

Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China.
Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China.
Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.

Hui Gao (H)

Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China.
Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China.
Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.

Xiaoqi Xu (X)

Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China.
Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China.
Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.

Guozhang Wang (G)

Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China.
Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China.
Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.

Weiwei Wang (W)

Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China.
Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China.
Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.

Xi Zhang (X)

Medical Center of Hematology, Xinqiao Hospital, Third Military Medical University, Chongqing, China.

Chunling Fu (C)

Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China.
Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China.
Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.

Kunming Qi (K)

Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China.
Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China.
Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.

Zhenyu Li (Z)

Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China.
Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.

Kailin Xu (K)

Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China. lihmd@163.com.
Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China. lihmd@163.com.

Jianlin Qiao (J)

Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China. jianlin.qiao@gmail.com.
Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China. jianlin.qiao@gmail.com.
Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China. jianlin.qiao@gmail.com.

Lingyu Zeng (L)

Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China. zengly2000@163.com.
Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China. zengly2000@163.com.
Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China. zengly2000@163.com.

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