PMID- 31479659
OWN - NLM
STAT- MEDLINE
DCOM- 20200226
LR  - 20200825
IS  - 1096-0945 (Electronic)
IS  - 0014-4800 (Linking)
VI  - 111
DP  - 2019 Dec
TI  - Long-term diabetes causes molecular alterations related to fibrosis and apoptosis 
      in rat urinary bladder.
PG  - 104304
LID - S0014-4800(19)30049-8 [pii]
LID - 10.1016/j.yexmp.2019.104304 [doi]
AB  - Diabetes induces time-dependent alterations in urinary bladders. Long-term 
      diabetes causes an underactive bladder. However, the fundamental mechanisms are 
      still elusive. This study aimed to examine the histological changes and the 
      potential molecular pathways affected by long-term diabetes in the rat bladder. 
      Diabetes was induced in 8-week-old male Lewis rats by streptozotocin, while 
      age-matched control rats received citrate buffer only. Forty-four weeks after 
      diabetes induction, bladders were harvested for histological and molecular 
      analyses. The expressions of proteins related to fibrosis, apoptosis and 
      oxidative stress as well as the cellular signaling pathway in the bladder were 
      examined by immunoblotting. Histological examinations illustrated diabetes caused 
      detrusor hypertrophy and fibrotic changes in the bladder. Immunoblotting analysis 
      demonstrated higher collagen I but lower elastin expression in the bladder in 
      diabetic rats. These were accompanied by an increase in the expression of 
      transforming growth factor-beta1, along with the downregulation of matrix 
      metalloptoteinase-1, and upregulation of tissue inhibitor of metalloproteinase-1. 
      Diabetic rats showed an increase in nitrotyrosine, but decrease in nuclear factor 
      erythroid-related factor 2 (Nrf2) levels in the bladder. Enhanced apoptotic 
      signaling was observed, characterized by increased expression of Bcl-2-associated 
      X protein (Bax), decreased expression of Bcl-2, in the diabetic bladder. The 
      nerve growth factor level was decreased in the diabetic bladder. A significant 
      suppression in the protein expressions of phosphorylated extracellular 
      signal-regulated kinases 1/2 was found in diabetic bladders. This study 
      demonstrated that long-term diabetes caused molecular changes that could promote 
      fibrosis and apoptosis in the bladder. Oxidative stress may be involved in this 
      context.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Elrashidy, Rania A
AU  - Elrashidy RA
AD  - Department of Surgery, MetroHealth Medical Center, Case Western Reserve 
      University, Cleveland, OH, USA; Department of Biochemistry, Faculty of Pharmacy, 
      Zagazig University, Zagazig, Egypt.
FAU - Liu, Guiming
AU  - Liu G
AD  - Department of Surgery, MetroHealth Medical Center, Case Western Reserve 
      University, Cleveland, OH, USA. Electronic address: guiming.liu@case.edu.
LA  - eng
GR  - R01 DK110567/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20190831
PL  - Netherlands
TA  - Exp Mol Pathol
JT  - Experimental and molecular pathology
JID - 0370711
RN  - 0 (Biomarkers)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Biomarkers/metabolism
MH  - Diabetes Mellitus, Experimental/*complications
MH  - Fibrosis/etiology/metabolism/*pathology
MH  - Male
MH  - *Oxidative Stress
MH  - Rats
MH  - Rats, Inbred Lew
MH  - Signal Transduction
MH  - Urinary Bladder/metabolism/*pathology
MH  - Urinary Bladder Diseases/etiology/metabolism/*pathology
OTO - NOTNLM
OT  - Bladder
OT  - Cystopathy
OT  - Diabetes
EDAT- 2019/09/04 06:00
MHDA- 2020/02/27 06:00
CRDT- 2019/09/04 06:00
PHST- 2019/01/18 00:00 [received]
PHST- 2019/07/23 00:00 [revised]
PHST- 2019/08/30 00:00 [accepted]
PHST- 2019/09/04 06:00 [pubmed]
PHST- 2020/02/27 06:00 [medline]
PHST- 2019/09/04 06:00 [entrez]
AID - S0014-4800(19)30049-8 [pii]
AID - 10.1016/j.yexmp.2019.104304 [doi]
PST - ppublish
SO  - Exp Mol Pathol. 2019 Dec;111:104304. doi: 10.1016/j.yexmp.2019.104304. Epub 2019 
      Aug 31.