title: MiR218 Modulates Wnt Signaling in Mouse Cardiac Stem Cells by Promoting Proliferation and Inhibiting Differentiation through a Positive Feedback Loop.
abstract: MiRNA expression was determined in both proliferating and differentiated cardiac stem cells (CSCs) through a comprehensive miRNA microarray analysis. We selected miR218 for functional follow-up studies to examine its significance in CSCs. First, we observed that the expression of miR218 was altered in CSCs during differentiation into cardiomyocytes, and transfection of an miR218 mimic or miR218 inhibitor affected the myocardial differentiation of CSCs. Furthermore, we observed that a negative regulator of Wnt signaling, sFRP2, was a direct target of miR218, and the protein levels of sFRP2 were increased in cells transfected with the synthetic miR218 inhibitor. In contrast, transfection with the miR218 mimic decreased the expression of sFRP2 and potentiated Wnt signaling. The subsequent down-regulation of sFRP2 by shRNA potentiated Wnt signaling, contributing to a gene expression program that is important for CSC proliferation and cardiac differentiation. Specifically, canonical Wnt signaling induced miR218 transcription. Thus, miR218 and Wnt signaling were coupled through a feed-forward positive feedback loop, forming a biological regulatory circuit. Together, these results provide the first evidence that miR218 plays an important role in CSC proliferation and differentiation through the canonical Wnt signaling pathway.
authors: Cardiology Department, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.|Key Laboratories of the Education Ministry for Myocardial Ischemia Mechanisms and Treatment, Harbin, Heilongjiang Province, China.
authors: Yongshun
authors: Y
authors: Wang
authors: Cardiology Department, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.|Key Laboratories of the Education Ministry for Myocardial Ischemia Mechanisms and Treatment, Harbin, Heilongjiang Province, China.
authors: Jingjin
authors: J
authors: Liu
authors: Cardiology Department, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.|Key Laboratories of the Education Ministry for Myocardial Ischemia Mechanisms and Treatment, Harbin, Heilongjiang Province, China.
authors: Jinjin
authors: J
authors: Cui
authors: Cardiology Department, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.|Key Laboratories of the Education Ministry for Myocardial Ischemia Mechanisms and Treatment, Harbin, Heilongjiang Province, China.
authors: Meng
authors: M
authors: Sun
authors: Cardiology Department, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.|Key Laboratories of the Education Ministry for Myocardial Ischemia Mechanisms and Treatment, Harbin, Heilongjiang Province, China.
authors: Wenjuan
authors: W
authors: Du
authors: Cardiology Department, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.|Key Laboratories of the Education Ministry for Myocardial Ischemia Mechanisms and Treatment, Harbin, Heilongjiang Province, China.
authors: Tao
authors: T
authors: Chen
authors: Cardiology Department, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.|Key Laboratories of the Education Ministry for Myocardial Ischemia Mechanisms and Treatment, Harbin, Heilongjiang Province, China.
authors: Xing
authors: X
authors: Ming
authors: Cardiology Department, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.|Key Laboratories of the Education Ministry for Myocardial Ischemia Mechanisms and Treatment, Harbin, Heilongjiang Province, China.
authors: Lulu
authors: L
authors: Zhang
authors: Cardiology Department, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.|Key Laboratories of the Education Ministry for Myocardial Ischemia Mechanisms and Treatment, Harbin, Heilongjiang Province, China.
authors: Jiangtian
authors: J
authors: Tian
authors: Cardiology Department, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.|Key Laboratories of the Education Ministry for Myocardial Ischemia Mechanisms and Treatment, Harbin, Heilongjiang Province, China.
authors: Ji
authors: J
authors: Li
authors: Cardiology Department, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.|Key Laboratories of the Education Ministry for Myocardial Ischemia Mechanisms and Treatment, Harbin, Heilongjiang Province, China.
authors: Li
authors: L
authors: Yin
authors: Cardiology Department, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.|Key Laboratories of the Education Ministry for Myocardial Ischemia Mechanisms and Treatment, Harbin, Heilongjiang Province, China.
authors: Fang
authors: F
authors: Liu
authors: Cardiology Department, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.|Key Laboratories of the Education Ministry for Myocardial Ischemia Mechanisms and Treatment, Harbin, Heilongjiang Province, China.
authors: Zhongyue
authors: Z
authors: Pu
authors: Cardiology Department, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.|Key Laboratories of the Education Ministry for Myocardial Ischemia Mechanisms and Treatment, Harbin, Heilongjiang Province, China.
authors: Bo
authors: B
authors: Lv
authors: Cardiology Department, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.|Key Laboratories of the Education Ministry for Myocardial Ischemia Mechanisms and Treatment, Harbin, Heilongjiang Province, China.
authors: Jingbo
authors: J
authors: Hou
authors: Cardiology Department, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.|Key Laboratories of the Education Ministry for Myocardial Ischemia Mechanisms and Treatment, Harbin, Heilongjiang Province, China.
authors: Bo
authors: B
authors: Yu
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation; D016000:Cluster Analysis; D025461:Feedback, Physiological; D020869:Gene Expression Profiling; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics; D051379:Mice; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D024510:Muscle Development / Q000235:genetics; D032386:Myoblasts, Cardiac / Q000166:cytology* / Q000378:metabolism*; D034622:RNA Interference; D060449:Wnt Signaling Pathway; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D008565:Membrane Proteins; D035683:MicroRNAs; C547684:MIRN218 microRNA, mouse; C109618:SFRP2 protein, human; D000094742:Secreted Frizzled-Related Proteins