The Mechanoreceptor TRPV4 is Localized in Adherence Junctions of the Human Bladder Urothelium: A Morphological Study

被引:70
作者
Janssen, Dick A. W.
Hoenderop, Joost G. [1 ,2 ]
Jansen, Kees C. F. J.
Kemp, Annemiete W. [1 ,2 ]
Heesakkers, John P. F. A.
Schalken, Jack A.
机构
[1] Radboud Univ Nijmegen, Med Ctr, Dept Urol, NL-6525 ED Nijmegen, Netherlands
[2] Radboud Univ Nijmegen, Med Ctr, Dept Physiol, NL-6525 ED Nijmegen, Netherlands
关键词
urinary bladder; overactive; urothelium; TRPV4; protein; human; catenins; RECEPTOR POTENTIAL VANILLOID-4; MICE LACKING; SENSORY ROLE; CHANNEL; EXPRESSION; CONTRIBUTES; ACTIVATION; CARCINOMA; ATP;
D O I
10.1016/j.juro.2011.04.107
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Purpose: TRPV4 (transient receptor potential vanilloid 4 channel) is a nonselective cation channel involved in different sensory functions that was recently implicated in bladder mechanosensation. We investigated the cellular site of TRPV4 in bladder urothelium and explored a molecular connection between TRPV4 and urothelial adherence junctions. Materials and Methods: We obtained healthy tissues sections from cystectomy in humans due to cancer in 3 and noncancerous conditions in 2. Besides human biopsies tissues from 7 normal and 7 TRPV4-/-mice, and the urothelial cell line RT4 were also used. Experiments were done with polyclonal antibody against TRPV4 (against the N-terminus of rat TRPV4). A molecular connection between TRPV4 and different adherence junction components was investigated using immunofluorescence, Western blot and immunoprecipitation. Results: Results revealed TRPV4 on urothelial cell membranes near adherence junctions. Results were comparable in the urothelial cell line, human bladders and mouse bladders. Subsequent immunoprecipitation experiments established a molecular connection of TRPV4 to alpha-catenin, an integral part of the adherence junction that catenates E-cadherin to the actin-microfilament network. Conclusions: Results provide evidence for the location of TRPV4 in human bladder urothelium. TRPV4 is molecularly connected to adherence junctions on the urothelial cell membrane. TRPV4 coupling to a rigid intracellular and intercellular structural network would agree with the hypothesis that TRPV4 can be activated by bladder stretch.
引用
收藏
页码:1121 / 1127
页数:7
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