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Eur Urol. 2009 Feb;55(2):491-7. doi: 10.1016/j.eururo.2008.03.090. Epub 2008 Apr 3.

TGF-beta1 inhibits Cx43 expression and formation of functional syncytia in cultured smooth muscle cells from human detrusor.

Author information

1
Department of Urology, University of Leipzig, Leipzig, Germany. jochen.neuhaus@medizin.uni-leipzig.de

Abstract

BACKGROUND:

Human detrusor smooth muscle cells (hBSMCs) are coupled by connexin 43 (Cx43)-positive gap junctions to form functional syncytia. Gap junctional communication likely is necessary for synchronised detrusor contractions and is supposed to be altered in voiding disturbances. Other authors have shown that the pleiotropic cytokine TGF-beta1 upregulates Cx43 expression in human aortic smooth muscle cells.

OBJECTIVE:

In this study, we examined the TGF-beta1 effects on Cx43 expression in cultured hBSMCs.

DESIGN, SETTING, AND PARTICIPANTS:

hBSMC cultures, established from patients undergoing cystectomy, were treated with recombinant human TGF-beta1.

MEASUREMENTS:

Cx43 expression was then examined by Western blotting, real-time PCR, and immunocytochemistry. Dye-injection experiments were used to study the size of functional syncytia.

RESULTS AND LIMITATIONS:

Dye-coupling experiments revealed stable formation of functional syncytia in passaged cell cultures (P1-P4). Stimulation with TGF-beta1 led to significant reduction of Cx43 immunoreactivity and coupling. Cx43 protein expression was significantly downregulated and Cx43 mRNA was only 30% of the control level. Interestingly, low phosphorylation species of Cx43 were particularly affected.

CONCLUSIONS:

Our experiments demonstrated a significant down regulation of connexin 43 by TGF-beta1 in cultured hBSMCs. These findings support the view that TGF-beta1 is involved in the pathophysiology of urinary bladder dysfunction.

PMID:
18406048
DOI:
10.1016/j.eururo.2008.03.090
[Indexed for MEDLINE]

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