Platelet-derived growth factor-BB increases expression of connexin 43 in an extracellular-regulated protein kinase-dependent manner in bladder smooth muscle cells.
OBJECTIVE
To investigate whether platelet-derived growth factor-BB induces the upregulation of connexin 43 in bladder smooth muscle cells and to examine the involved signaling pathway.


METHODS
Bladder smooth muscle cells were exposed to platelet-derived growth factor-BB in the presence or absence of p38 mitogen-activated protein kinase, c-jun amino-terminal kinase or extracellular-regulated protein kinase inhibitors. Transfection of bladder smooth muscle cells with specific small interference ribonucleic acid against platelet-derived growth factor receptor-β gene expression was also carried out to investigate whether platelet-derived growth factor receptor-β was involved in the signaling pathway. Expression of messenger ribonucleic acid and protein for connexin 43 was measured by real time polymerase chain reaction and western blot.


RESULTS
The addition of platelet-derived growth factor-BB in cultured bladder smooth muscle cells caused the significant upregulation of connexin 43, and the activation of extracellular-regulated protein kinase, c-jun amino-terminal kinase and p38 mitogen-activated protein kinase compared with the control group. This action of platelet-derived growth factor-BB could be abolished by the pretreatment of bladder smooth muscle cells with the extracellular-regulated protein kinase inhibitor PD98059, whereas p38 mitogen-activated protein kinase and c-jun amino-terminal kinase inhibitors did not have any effect on this. Platelet-derived growth factor-BB could induce the activation of platelet-derived growth factor receptor-β. Transfection of bladder smooth muscle cells with small interference ribonucleic acid specific for platelet-derived growth factor receptor-β gene resulted in the potent suppression of gene expression and inhibition of extracellular-regulated protein kinase activation, as well as upregulation of connexin 43 induced by platelet-derived growth factor-BB.


CONCLUSIONS
Platelet-derived growth factor-BB upregulates connexin 43 expression through the activation of extracellular-regulated protein kinase and platelet-derived growth factor receptor-β signaling pathways. This finding suggests that this signaling pathway might provide a potential target to manipulate detrusor overactivity.
Urological Institution of the People's Liberation Army, First Affiliated Hospital of Third Military Medical University, Chongqing, China.
Wenhao
W
Shen
Longkun
L
Li
Bo
B
Song
Weibing
W
Li
Zhansong
Z
Zhou
Ruiwei
R
Guo
D000818:Animals; D002478:Cells, Cultured; D018031:Connexin 43 / Q000378:metabolism*; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D055785:Gene Knockdown Techniques; D020935:MAP Kinase Signaling System; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D015854:Up-Regulation; D053201:Urinary Bladder, Overactive / Q000378:metabolism*
D018031:Connexin 43; C580592:Gja1 protein, rat; D020574:Proto-Oncogene Proteins c-sis; D020797:Receptor, Platelet-Derived Growth Factor beta; D048049:Extracellular Signal-Regulated MAP Kinases