Abstract
CyclinD1 over-expression is the key pathogenetic event underlying airway smooth muscle (ASM) proliferation. Human antigen R (HuR) is a ubiquitously expressed RNA-binding protein, and is known to regulate the expression of multiple cell cycle regulators. The aim of the study is to investigate whether HuR might also be involved in ASM proliferation. In cultured ASM cells, PDGF treatment induced a significant elevation of HuR expression at both mRNA and protein levels. Immunofluorescence analysis demonstrated PDGF might promote HuR translocation from nucleus to cytoplasma as well. RNA-interference of HuR effectively decreased PDGF-induced cyclinD1 over-expression in ASM cells. Furthermore, AMPK activation by AICAR could effectively decrease PDGF-induced HuR cytoplasmatic translocation, cyclinD1 expression and ASM cells proliferation. In conclusion, altered expression and activity of HuR might participate in PDGF-induced ASM cells cyclinD1 expression and proliferation. The effectiveness of AMPK activation indicated a novel intervention method for airway remodeling.
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Abbreviations
- HuR:
-
Human antigen R
- ASM:
-
Airway smooth muscle
- PDGF:
-
Platelet-derived growth factor
- AMPK:
-
Amp-activated protein kinase
- ARE:
-
Adenosine and uracil (AU) rich element
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Acknowledgments
This work was supported by Shandong Natural Science Foundation (ZR2009CM043, ZR2009CQ034) and Shandong Doctoral Foundation of China (2006BS03030, BS2009YY020).
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Pengju Zhang and Mingfeng Cao contributed equally to the research.
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Zhang, P., Cao, M., Liu, Y. et al. PDGF-induced airway smooth muscle proliferation is associated with Human antigen R activation and could be weakened by AMPK activation. Mol Biol Rep 39, 5819–5829 (2012). https://doi.org/10.1007/s11033-011-1392-z
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DOI: https://doi.org/10.1007/s11033-011-1392-z