PDGF-induced airway smooth muscle proliferation is associated with Human antigen R activation and could be weakened by AMPK activation.
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.
Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, China.
Pengju
P
Zhang
Mingfeng
M
Cao
Yi
Y
Liu
Zhimei
Z
Lv
Qingrui
Q
Yang
Xiaoyan
X
Lin
Huaichen
H
Li
Qiang
Q
Wan
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism*; D001980:Bronchi / Q000166:cytology*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D021381:Protein Transport / Q000187:drug effects; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012265:Ribonucleotides / Q000494:pharmacology
D000954:Antigens, Surface; C530104:CCND1 protein, human; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D010982:Platelet-Derived Growth Factor; D016601:RNA-Binding Proteins; D012265:Ribonucleotides; D019938:Cyclin D1; D000620:Aminoimidazole Carboxamide; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide