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Toll-Like Receptor 4 Activation Contributes to Diabetic Bladder Dysfunction in a Murine Model of Type 1 Diabetes

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 hypercontractili...

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Autores principales: Szasz, Theodora, Wenceslau, Camilla F., Burgess, Beth, Nunes, Kenia P., Webb, R. Clinton
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5127246/
https://www.ncbi.nlm.nih.gov/pubmed/27650857
http://dx.doi.org/10.2337/db16-0480
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author Szasz, Theodora
Wenceslau, Camilla F.
Burgess, Beth
Nunes, Kenia P.
Webb, R. Clinton
author_facet Szasz, Theodora
Wenceslau, Camilla F.
Burgess, Beth
Nunes, Kenia P.
Webb, R. Clinton
author_sort Szasz, Theodora
collection PubMed
description 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 knockout (TLR4KO) mice were made diabetic by streptozotocin (STZ) treatment, and bladder contractile function and TLR4 pathway expression were evaluated. Immunohistochemistry confirmed the 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 bladders from STZ mice, and TLR4 inhibitor CLI-095 attenuated this increase. Induction of diabetes by STZ in WT mice increased bladder weight and contractile responses to CCh and to electrical field stimulation. TLR4KO mice were not protected from STZ-induced diabetes; however, despite levels of hyperglycemia similar to those of 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 and hypercontractility.
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spelling pubmed-51272462017-12-01 Toll-Like Receptor 4 Activation Contributes to Diabetic Bladder Dysfunction in a Murine Model of Type 1 Diabetes Szasz, Theodora Wenceslau, Camilla F. Burgess, Beth Nunes, Kenia P. Webb, R. Clinton Diabetes Complications 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 knockout (TLR4KO) mice were made diabetic by streptozotocin (STZ) treatment, and bladder contractile function and TLR4 pathway expression were evaluated. Immunohistochemistry confirmed the 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 bladders from STZ mice, and TLR4 inhibitor CLI-095 attenuated this increase. Induction of diabetes by STZ in WT mice increased bladder weight and contractile responses to CCh and to electrical field stimulation. TLR4KO mice were not protected from STZ-induced diabetes; however, despite levels of hyperglycemia similar to those of 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 and hypercontractility. American Diabetes Association 2016-12 2016-09-20 /pmc/articles/PMC5127246/ /pubmed/27650857 http://dx.doi.org/10.2337/db16-0480 Text en © 2016 by the American Diabetes Association. http://www.diabetesjournals.org/content/licenseReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.
spellingShingle Complications
Szasz, Theodora
Wenceslau, Camilla F.
Burgess, Beth
Nunes, Kenia P.
Webb, R. Clinton
Toll-Like Receptor 4 Activation Contributes to Diabetic Bladder Dysfunction in a Murine Model of Type 1 Diabetes
title Toll-Like Receptor 4 Activation Contributes to Diabetic Bladder Dysfunction in a Murine Model of Type 1 Diabetes
title_full Toll-Like Receptor 4 Activation Contributes to Diabetic Bladder Dysfunction in a Murine Model of Type 1 Diabetes
title_fullStr Toll-Like Receptor 4 Activation Contributes to Diabetic Bladder Dysfunction in a Murine Model of Type 1 Diabetes
title_full_unstemmed Toll-Like Receptor 4 Activation Contributes to Diabetic Bladder Dysfunction in a Murine Model of Type 1 Diabetes
title_short Toll-Like Receptor 4 Activation Contributes to Diabetic Bladder Dysfunction in a Murine Model of Type 1 Diabetes
title_sort toll-like receptor 4 activation contributes to diabetic bladder dysfunction in a murine model of type 1 diabetes
topic Complications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5127246/
https://www.ncbi.nlm.nih.gov/pubmed/27650857
http://dx.doi.org/10.2337/db16-0480
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