Toll-like receptor 4 mediates diabetic bladder dysfunction.
| Summary |
Data Summary |
| Investigator |
Webb, Clinton |
| Description |
Diabetes mellitus (DM) is at epidemic proportions in the U.S. with 18.8 million
people diagnosed and an estimated 7 million undiagnosed. Furthermore, 35% of
U.S. adults are pre-diabetic. Because DM affects every organ, patients with DM
suffer from several complications including lower urinary tract dysfunctions.
These complications are costly and diminish the quality of life of patients with
DM. Bladder dysfunction is among the most common complications of the lower
urinary tract in DM. Despite significant recent advances in understanding
diabetic bladder dysfunction, the underlying molecular pathways that initiate
this dysfunction are poorly understood, and therefore, the current treatments of
this complication are not always effective. Activation of Toll-like receptors
(TLR), receptors of the innate immune system, has been shown to play a role in
the development of DM. For example, hyperglycemia induces the expression and
activation of TLR4, leading to inflammation and oxidative stress, both
components of the pathology of DM. Furthermore, patients with DM are prone to
urinary and bladder infections, which can induce the activation of TLR4 via
pathogen-associated molecular patterns expressed by bacteria. Nevertheless, it
is currently unknown whether activation of TLR4 leads to bladder dysfunction and
whether a hyperglycemic environment potentiates the role of the innate immune
system in diabetic bladder complications. Accordingly, we propose the innovative
hypothesis that hyperglycemia leads to TLR4 activation, which causes bladder
smooth muscle hypertrophy and hypercontractility, characteristics of the
diabetic overactive bladder. Two aims are proposed for this study: Specific aim
1 will determine whether hyperglycemia activates TLR4 to increase cell
proliferation and reactive oxygen species (ROS) production in mouse bladder
smooth muscle cells. Specific aim 2 will determine whether bladder hypertrophy
and hypercontractility in diabetes is mediated
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| Status |
Completed |
| Public Release |
10/28/2016 |
| Data Collected? |
Data will not be collected for this catalog item |
| Species |
M. musculus |
| Animal Age |
Measured In: week(s) post-natal (w) |
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| Data Analysis |
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| Type | Count | Released |
| Animals | 0 | - |
| Experimental Conditions | 0 | - |
| Phenotype Assays | 0 | - |
| Phenotype Measurements | 0 | 0 |
| Microarrays | 0 | - |
| Histology Images | 0 | 0 |
| Publications | 0 | - |
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Experimental Factor Values