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. 2016 Jun;11(6):2139-2146.
doi: 10.3892/etm.2016.3246. Epub 2016 Apr 11.

Structural and functional changes in gap junctional intercellular communication in a rat model of overactive bladder syndrome induced by partial bladder outlet obstruction

Fenghai Zhou  1 , Haiyuan Li  2 , Chuan Zhou  3 , Haidi Lv  1 , Yulei Ma  2 , Yangmin Wang  1 , B O Song  4
Affiliations

Structural and functional changes in gap junctional intercellular communication in a rat model of overactive bladder syndrome induced by partial bladder outlet obstruction

Fenghai Zhou et al. Exp Ther Med. 2016 Jun.

Abstract

The aim of the present study was to investigate the association between connexin (Cx)43 levels and alterations in gap junctional mediation of intercellular communication in overactive bladder syndrome (OAB), and to examine the effects of connexin inhibitor on this condition. Adult female Wistar rats with OAB following partial bladder outlet obstruction (PBBO) (OAB group, n=37) and sham-operated rats (control group, n=17) were studied. The ultrastructure of the rat detrusor was observed by transmission electron microscopy and the protein expression levels of Cx43 were analyzed using western blot analysis. Furthermore, bladder detrusor cells in both groups were cultured and cells in the OAB group were randomly divided into ten groups. In nine of these groups, 18-β glycyrrhetinic acid (18β-GA) was administered at various doses and durations. All groups were compared using fluorescence redistribution after photobleaching and a laser scanning confocal microscope. Cystometry demonstrated that gap junctions were an abundant mechanism among adjacent cells, and Cx43 protein expression levels were increased in the OAB group following 6 weeks of obstruction, as compared with the control group. Mean fluorescence recovery rates in the OAB group were significantly increased, as compared with the control group (P<0.01). Mean fluorescence recovery rates were noted following 18β-GA administration. These results suggested that upregulation of Cx43 induces structural and functional alterations in gap junctional intercellular communication following PBOO, and connexin inhibitors may be a novel therapeutic strategy for the clinical treatment of OAB.

Keywords: 18β-GA; connexin 43; gap junctional intercellular communication; overactive bladder syndrome.

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Figures

Figure 1.
Figure 1.
Observation with electron microscope (magnification, ×6,000). (A) Abundant gap junctions (arrowhead) were detected in the OAB group samples; whereas (B) Intermediate junction (arrowhead) were detected in the control samples. OAB, overactive bladder syndrome.
Figure 2.
Figure 2.
Western blot analysis of Cx43 expression levels in bladder detrusor. (A) Lane 1, LMw marker; lane 2, OAB group; and lane 3, control group. (B) Cx43 expression levels in bladder detrusor, as quantified by densitometry. **P<0.01 vs. the control group. OAB, overactive bladder syndrome.
Figure 3.
Figure 3.
Gap junctional intercellular communication in detrusor smooth muscle cells in the overactive bladder syndrome group, as demonstrated by fluorescence redistribution after photobleaching. The arrows indicate the bleached cells. Images were captured (A) prior to bleaching and after bleaching at (B) 0, (C) 2 and (D) 4 min.
Figure 4.
Figure 4.
Gap junctions in detrusor cells of the control group, as demonstrated by fluorescence redistribution after photobleaching. The arrows indicate the bleached cells. Images were captured (A) prior to bleaching and after bleaching at (B) 0, (C) 2 and (D) 4 min.
Figure 5.
Figure 5.
Fluorescence intensity of bleaching cell of bladder detrusor at various time points. Data are presented as the mean ± standard deviation. *P<0.05 vs. the control group,**P<0.01 vs. the control group. OAB, overactive bladder syndrome.
Figure 6.
Figure 6.
Mean fluorescence recovery rates of bladder detrusor cells at 4 min in the OAB and control groups. Data are presented as the mean ± standard deviation. **P<0.01 vs. the control group. OAB, overactive bladder syndrome.
Figure 7.
Figure 7.
Mean fluorescence recovery rates in the OAB group in the presence of 18β-GA at various concentrations. Data are presented as the mean ± standard deviation. P<0.01 for 18β-GA at 10 µmol/l at 1 and 2 min vs. the corresponding OAB group; P<0.05 for 18β-GA at 10 µmol/l at 3 and 4 min vs. the corresponding OAB group; P<0.01 for 18β-GA at 20, 40, 80 and 160 µmol/l at all time points vs. the corresponding OAB group. OAB, overactive bladder syndrome.
Figure 8.
Figure 8.
Mean fluorescence recovery rates (4 min) of cells in the OAB and control groups in the presence of the same 18β-GA concentration (40 µmol/l) at various time points. Data are presented as the mean ± standard deviation. OAB, overactive bladder syndrome.
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