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Simulated Bladder Pressure Stimulates Human Bladder Smooth Muscle Cell Proliferation via the PI3K/SGK1 Signaling Pathway.
MedLine Citation:
PMID:  22704443     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
PURPOSE: A mechanical stimulus on detrusor tissue is critical to bladder outlet obstruction progression and functional bladder tissue engineering. A hypothesis is that mechanical stimulus triggers human bladder smooth muscle cell proliferation. To help better understand this relationship of bladder function to growth at the cellular level we used a novel method of applying cyclic hydrodynamic pressure that simulates the bladder cycle to cell cultures. We detected the proliferation response of human bladder smooth muscle cells (4310, ScienCell™) to different pressures as well as the signal transduction mechanism of this process. MATERIALS AND METHODS: Human bladder smooth muscle cells cultured in scaffolds underwent 4 pressures (0, 100, 200 and 300 cm H(2)O) for 24 hours, as controlled by a BioDynamic® bioreactor. We then used flow cytometry to examine cell cycle distribution, and polymerase chain reaction and immunoblot to quantify SGK1 and AKT expression and activation in each group. SGK1 was silenced in human bladder smooth muscle cells using small interfering RNA to validate the role of SGK1 in mediating pressure induced cell proliferation. RESULTS: Compared with the 0 cm H(2)O control group, human bladder smooth muscle cells in the 200 and 300 cm H(2)O groups showed increased cell proliferation. SGK1 expression and activity were also increased while AKT, another downstream signal of PI3K, did not change significantly. SGK1 silencing abolished the increases in cell proliferation induced by pressure. CONCLUSIONS: To our knowledge we provide the first report of cyclic hydrodynamic pressure stimulating the proliferation of human bladder smooth muscle cells cultured in scaffolds. The signal transduction mechanism for this process is involved with the PI3K/SGK1 and not the PI3K/AKT signaling pathway.
Authors:
Lin Chen; Tang-Qiang Wei; Yan Wang; Jie Zhang; Hong Li; Kun-Jie Wang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-14
Journal Detail:
Title:  The Journal of urology     Volume:  -     ISSN:  1527-3792     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-6-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376374     Medline TA:  J Urol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
Affiliation:
Department of Urology and Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
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