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MP94-12: Bladder Outlet Obstruction induced remodeling of extracellular matrix of human bladder smooth muscle cells via IL-6

Tuesday, May 16
7:00 AM - 9:00 AM
Location: BCEC: Room 253AB

Presentation Authors: Yifei Lin*, Kunjie Wang, Chengdu, China, People's Republic of

Introduction: Bladder Outlet Obstruction(BOO) is one of the pathological changes resulted from abnormal intravesical pressure. We investigated the effects of hydrostatic pressure and mechanic strain on the release of inflammatory cytokines in rat and human bladder smooth muscle cells (HBSMCs) and tried to explore the relationship of Il-6 and the remodeling of of extracellular matrix of human bladder smooth muscle cells.

Methods: Animal model of bladder outlet obstruction was induced by urethra ligation. HBSMCs were subjected to elevated hydrostatic pressure and mechanic strain. The expression of inflammatory genes were analysed using DNA microarrays. IL-6 was confirmed by quantitative RT-PCR and immunohistochemical staining. Specificity of the IL-6 was determined with qRT-PCR with small interfering ribonucleic acid transfection and iL-6 receptor inhibitor (SC144). And specificity of the  downstream was determined with qRT-PCR with small interfering ribonucleic acid transfection and STAT3 inhibitor(S31-201).


Results: In BOO, inflammatory genes were remarkably induced. in vitro, the expressions of IL-6 were significantly increased. Hydrostatic pressure and mechanic strain both promoted the IL-6 mRNA expression. Additionally, IL-6 increased the mRNA expression of MMP7 and TIMP1, decreased the mRNA expression of collagen and fibronectin. The "knock- down" of activation of IL-6 receptor using target small interfering ribonucleic acid transfection and inhibitor iL-6 receptor(SC144) significantly decreased the expression of MMP7 ,TIMP1 and partially increased the collagen and fibronectin. Additionally, pressure-induced MMP7 andTIMP1 were partially suppressed by STAT3 pathway using target small interfering ribonucleic acid transfection and inhibitor STAT3 (S31-201).

Conclusions: IL-6 was involved in the remodeling of extracellular matrix in HBSMCs under mechanic strain and hydrostatic pressure, indicating that IL-6 play an important role under in BOO.

Source Of Funding: This study was supported by Grant No. 31170907, No. 31370951, No. 81470927 and No.81300579 from the National Natural Science Foundation of China, Grant No. 2014SCU04B21 from Fund for Distinguished Young Scholars of Sichuan University, Grant No.JH2014053

Yifei Lin, MD

Department of Urology/ Institute of Urology, West China Hospital, Sichuan University

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MP94-12: Bladder Outlet Obstruction induced remodeling of extracellular matrix of human bladder smooth muscle cells via IL-6



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