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Role of Interstitial Cells in Diabetic Bladder Dysfunction
Summary Data Summary
Applicant Koh, Sang
E-Mail Address skoh@medicine.nevada.edu
Project Title Role of Interstitial Cells in Diabetic Bladder Dysfunction
CBU ID 13GHSU267
External SubContract ID 25732-18
Diabetic Complication Uropathy
Funding Program Group Pilot & Feasibility [PF2013]
Abstract Diabetic bladder dysfunction (DBD) is the most common and costly complications
of Diabetes Mellitus (DM). Estimates of the prevalence of DBD range from 25% to
83%. DM causes the bladder to undergo 2 phases of alterations. Early phase DBD
manifests as storage problems such as urgency and urge incontinence at the
clinical level. Late phase DBD manifests as voiding problems, leading to bladder
inability to empty. The pathophysiology of overactive bladder of early phase DBD
is due to increased phasic activity in the bladder smooth muscle of animal
models and patients with detrusor overactivity. However the exact
pathophysiological mechanism of increased detrusor responsiveness in early stage
DBD is divergent and unclear. In this proposal we will focus on the changes in
function and phenotype of detrusor smooth muscle to understand the mechanism of
early DBD. We will use two types of animal models, streptozotocin (STZ)-induced
type 1DM and high fat-diet induced type 2 DM mice.
We have recently discovered a novel type of interstitial cells in detrusor
muscles. These cells were identified with antibodies against platelet-derived
growth factor receptor-alpha ?(PDGFRa). PDGFRa+ cells have been identified in
human, guinea pig and murine detrusor muscle. PDGFRa+ cells are associated with
varicose nerve processes in detrusor muscles5. Thus, PDGFRa+ cells may be
innervated and receive and transduce neurotransmitters. small-conductance
Ca2+-activated K+ (SK) channels are known to be involved in membrane
stabilization in the detrusor. SK channels were reported in detrusor smooth
muscle cells (SMCs). However, the current density attributable to SK channels in
detrusor SMC is minimal. In contrast, PDGFRa+ cells display a very high current
density attributable to SK channels. Defects of SK channels in PDGFRa+ cells
amplify contractile responses leading to a detrusor overactivity phenotype.
Thus, we will characterize the molecular and protein components of these novel
PDGFRa+ cells and determine how these cells participate in the regulation of
DBD. The results will provide information about the function of PDGFRa+ cells in
the detrusor and serve as a baseline for evaluations of function and plasticity
of these cells in early stage DBD.
Application PDF Application Research Plan
Status Contract Executed
Key Personnel
Salary Total Costs 57794
Supply Total Costs 11892
Equipment Total Costs 0
Travel/Other Total Costs 0
Direct Costs 69686
Indirect Costs Proposed 30314
Total Costs Proposed 100000
Total Costs Approved 100000
Start Date 10/1/2013
End Date 9/30/2014
IFO Name Smith, Karen
IFO E-Mail Address ospadmin@unr.edu
IACUC/IRB No. #00437
IACUC/IRB Institution University of Nevada-Reno
Entity ID No. 188-600002A1
Report Request Date 10/30/2014
T1D NO
TypeCount
Invoices 10
Progress Reports 1
Data Submission


Invoices
UrlCBU IDExternal IDInstitutionDateDirectIndirectInvoiceBalancePDF
  View  13GHSU26725732-18University of Nevada-Reno9/16/2014$17,093.61-$17,093.61$2,609.86View PDF
  View  13GHSU26725732-18University of Nevada-Reno8/20/2014$5,773.78-$5,773.78$2,609.86View PDF
  View  13GHSU26725732-18University of Nevada-Reno7/15/2014$8,013.15-$8,013.15$2,609.86View PDF
  View  13GHSU26725732-18University of Nevada-Reno6/25/2014$5,021.71-$5,021.71$2,609.86View PDF
  View  13GHSU26725732-18University of Nevada-Reno5/22/2014$7,984.21-$7,984.21$2,609.86View PDF
  View  13GHSU26725732-18University of Nevada-Reno4/26/2017---$2,609.86 
  View  13GHSU26725732-18University of Nevada-Reno4/16/2014$7,265.06-$7,265.06$2,609.86View PDF
  View  13GHSU26725732-18University of Nevada-Reno3/11/2014$3,658.79$1,591.57$5,250.36$2,609.86View PDF
  View  13GHSU26725732-18University of Nevada-Reno2/27/2014$722.58$314.32$1,036.90$2,609.86View PDF
  View  13GHSU26725732-18University of Nevada-Reno11/3/2014$42,560.62-$42,560.62$2,609.86View PDF


Reports
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