Tissue specific dysregulated protein subnetworks in type 2 diabetic bladder
urothelium and detrusor muscle.
Authors Tomechko SE, Liu G, Tao M, Schlatzer D, Powell CT, Gupta S, Chance MR,
Daneshgari F
Submitted By Firouz Daneshgari on 3/4/2015
Status Published
Journal Molecular & cellular proteomics : MCP
Year 2015
Date Published 1/8/2015
Volume : Pages Not Specified : Not Specified
PubMed Reference 25573746
Abstract Diabetes mellitus is well known to cause bladder dysfunction; however, the
molecular mechanisms governing this process and the effects on individual tissue
elements within the bladder are poorly understood, particularly in type 2
diabetes. A shotgun proteomics approach was applied to identify proteins
differentially expressed between type 2 diabetic (TallyHo) and control (SWR/J)
mice in the bladder smooth muscle and urothelium, separately. We were able to
identify 1760 non-redundant proteins from the detrusor smooth muscle and 3169
non-redundant proteins from urothelium. Pathway and network analysis of
significantly dysregulated proteins was conducted to investigate the molecular
processes associated with diabetes. This pinpointed ERK1/2 signaling as a key
regulatory node in the diabetes-induced pathophysiology for both tissue types.
The detrusor muscle samples showed diabetes-induced increased tissue
remodeling-type events such as Actin Cytoskeleton Signaling and Signaling by Rho
Family GTPases. The diabetic urothelium samples exhibited oxidative stress
responses, as seen in the suppression of protein expression for key players in
the NRF2-Mediated Oxidative Stress Response pathway. These results suggest that
diabetes induced elevated inflammatory responses, oxidative stress, and tissue
remodeling are involved in the development of tissue specific diabetic bladder
dysfunctions. Validation of signaling dysregulation as a function of diabetes
was performed using Western blotting. These data illustrated changes in ERK1/2
phosphorylation as a function of diabetes, with significant decreases in
diabetes-associated phosphorylation in urothelium, but the opposite effect in
detrusor muscle. These data highlight the importance of understanding tissue
specific effects of disease process in understanding pathophysiology in complex
disease and pave the way for future studies to better understand important
molecular targets in reversing bladder dysfunction.

Investigators with authorship
Firouz DaneshgariCase Western Reserve
Guiming LiuCase Western Reserve