Interaction of Caveolin-3 and HCN is involved in the pathogenesis of diabetic cystopathy.
A growing body of research suggests that impaired bladder Cajal-like interstitial cells (ICCs) are a important component in the pathogenesis of diabetes-induced bladder dysfunction, although the molecular mechanisms have not been illustrated completely. The purpose of this study was to examine whether the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in ICCs-DM were responsible for the detrusor weak contractility of Diabetic cystopathy (DCP) and to study the possible mechanism of regulating the expression and function of HCN channels. HCN channels expression were decreased at the mRNA and protein levels. Forskolin (FSK), which can elevate intracellular cAMP levels, increased the density of the hyperpolarization-activated current and intracellular calcium concentration in both normal control (NC) rats and DCP rats, but the sensitivity of FSK on HCN channels was clearly down-regulated in DCP rats. The loss of caveolae and caveolin was in accordance with the decrease in HCN channels. Caveolin-3 co-localizes with and affects the expression and function of HCN. Taken together, these results indicate that the loss of caveolae and HCN channels in ICCs-DM is important in the pathogenesis of DCP. Increasing the number of caveolae to enhance the function of HCN channels may represent a viable target for the pharmacological treatment of DCP.
Department of Urology, Second Affiliated Hospital, Third Military Medical University, Chongqing, China.
Xingyou
X
Dong
Department of Biomedical Engineering, the Cleveland Clinic, Cleveland, OH, United States of America.
Qixiang
Q
Song
Department of Urology, Second Affiliated Hospital, Third Military Medical University, Chongqing, China.
Jingzhen
J
Zhu
Department of Urology, Second Affiliated Hospital, Third Military Medical University, Chongqing, China.
Jiang
J
Zhao
Department of Urology, Second Affiliated Hospital, Third Military Medical University, Chongqing, China.
Qian
Q
Liu
Department of Urology, Second Affiliated Hospital, Third Military Medical University, Chongqing, China.
Teng
T
Zhang
Department of Urology, Second Affiliated Hospital, Third Military Medical University, Chongqing, China.
Zhou
Z
Long
Department of Urology, Second Affiliated Hospital, Third Military Medical University, Chongqing, China.
Jia
J
Li
Department of Urology, Second Affiliated Hospital, Third Military Medical University, Chongqing, China.
Chao
C
Wu
Department of Urology, Second Affiliated Hospital, Third Military Medical University, Chongqing, China.
Qingqing
Q
Wang
Department of Urology, Second Affiliated Hospital, Third Military Medical University, Chongqing, China.
Xiaoyan
X
Hu
Department of Biomedical Engineering, the Cleveland Clinic, Cleveland, OH, United States of America.
Margot
M
Damaser
Department of Urology, Second Affiliated Hospital, Third Military Medical University, Chongqing, China.
Longkun
L
Li
D000818:Animals; D051244:Caveolin 3 / Q000235:genetics / Q000378:metabolism*; D048909:Diabetes Complications / Q000503:physiopathology*; D020869:Gene Expression Profiling; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D001745:Urinary Bladder Diseases / Q000503:physiopathology*
D051244:Caveolin 3; C578667:Hcn1 protein, rat; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D015221:Potassium Channels; D012333:RNA, Messenger