Crif1 Promotes Adipogenic Differentiation of Bone Marrow Mesenchymal Stem Cells After Irradiation by Modulating the PKA/CREB Signaling Pathway

被引：24

作者：

Zhang, Xi ^{[1
]}

Xiang, Lixin ^{[2
]}

Ran, Qian ^{[2
]}

Liu, Yao ^{[1
]}

Xiang, Yang ^{[2
]}

Xiao, Yanni ^{[2
]}

Chen, Li ^{[2
]}

Li, Fengjie ^{[2
]}

Zhong, Jiang F. ^{[3
]}

Li, Zhongjun ^{[2
]}

机构：

[1] Third Mil Med Univ, Affiliated Hosp 2, Dept Hematol, Chongqing, Peoples R China

[2] Third Mil Med Univ, Affiliated Hosp 2, Dept Blood Transfus, Chongqing, Peoples R China

[3] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA

来源：

STEM CELLS | 2015年 / 33卷 / 06期

基金：

中国国家自然科学基金;

关键词：

Bone marrow mesenchymal stem cells; Adipogenesis; Radiation; Protein kinase A; CR6-INTERACTING FACTOR-1 INTERACTS; DEPENDENT PROTEIN-KINASE; IN-VIVO; RADIATION; ADIPOCYTE; CREB; MICROENVIRONMENT; PHOSPHORYLATION; OSTEOGENESIS; SENSITIVITY;

D O I：

10.1002/stem.2019

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Dysfunction of the hematopoietic microenvironment is the main obstacle encountered during hematopoiesis reconstruction in patients with acute hematopoietic radiation syndrome. Bone marrow mesenchymal stem cells (BM-MSCs) play a crucial supporting role in hematopoiesis by maintaining the balance between adipogenic and osteogenic differentiation. In this study, we found that irradiation decreased the colony-forming efficiency of BM-MSCs and impaired the balance between adipogenic and osteogenic differentiation. Following irradiation, BM-MCSs became strongly predisposed to adipogenesis, as evidenced by increased oil red O staining and elevated mRNA and protein levels of the adipogenic markers and transcription factors PPAR and AP2. Overexpression of the essential adipogenesis regulator Crif1 in BM-MSCs promoted adipogenesis after irradiation exposure by upregulating adipogenesis-related genes, including C/EBP, PPAR, and AP2. We found that Crif1 promoted the phosphorylation of cAMP response element binding protein (CREB) through direct interaction with protein kinase A (PKA)-. Phosphorylation of CREB was inhibited in Crif1-knockdown BM-MSCs even in the presence of a PKA agonist (db-cAMP) and could be suppressed in Crif1-overexpressing BM-MSCs by a PKA inhibitor (H-89). These results suggest that Crif1 is an indispensable regulator of PKA cat that modulates the PKA/CREB signaling pathway to promote adipogenic differentiation of BM-MSCs after irradiation. Stem Cells2015;33:1915-1926

引用

页码：1915 / 1926

页数：12

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