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Toll-Like Receptor 4 Activation Contributes to Diabetic Bladder Dysfunction in a
Murine Model of Type I Diabetes.
Szasz T, Wenceslau CF, Burgess B, Nunes KP, Webb RC
Clinton Webb on 9/28/2016
Volume : Pages
Diabetic bladder dysfunction (DBD) is a common urological complication of
diabetes. Innate immune system activation via Toll-like receptor 4 (TLR4) leads
to inflammation and oxidative stress and was implicated in diabetes
pathophysiology. We hypothesized that bladder hypertrophy and hypercontractility
in DBD is mediated by TLR4 activation. Wild type (WT) and TLR4 knock-out
(TLR4KO) mice were made diabetic by streptozotocin (STZ) treatment and bladder
contractile function and TLR4 pathway expression were evaluated.
Immunohistochemistry confirmed expression of TLR4 in human and mouse bladder.
Recombinant high mobility group box protein 1 (HMGB1) increased bladder TLR4 and
MyD88 expression and enhanced contractile response to electrical field
stimulation. Bladder expression of TLR4 and MyD88 and serum expression of HMGB1
were increased in STZ compared with control mice. Carbachol (CCh)-mediated
contraction was increased in bladder from STZ mice and TLR4 inhibitor CLI-095
attenuated this increase. STZ diabetes induction in WT mice increased bladder
weight and contractile responses to CCh and electrical field stimulation. TLR4KO
mice were not protected from STZ-induced diabetes, however, despite similar
levels of hyperglycemia as WT STZ mice, TLR4KO STZ mice were protected from
diabetes-induced bladder hypertrophy and hypercontractility. These data suggest
that TLR4 activation during diabetes mediates DBD-associated bladder hypertrophy
Neuropathy & Neurocognition
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Please acknowledge all posters, manuscripts or scientific materials that were generated in part or whole using funds from the Diabetic Complications Consortium(DiaComp) using the following text:
Financial support for this work provided by the NIDDK Diabetic Complications Consortium (RRID:SCR_001415, www.diacomp.org), grants DK076169 and DK115255
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