PMID- 27830089
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231104
IS  - 2090-214X (Print)
IS  - 2090-2158 (Electronic)
VI  - 2016
DP  - 2016
TI  - Proteasome Activators, PA28alpha and PA28beta, Govern Development of Microvascular 
      Injury in Diabetic Nephropathy and Retinopathy.
PG  - 3846573
LID - 3846573
AB  - Diabetic nephropathy (DN) and diabetic retinopathy (DR) are major complications 
      of type 1 and type 2 diabetes. DN and DR are mainly caused by injury to the 
      perivascular supporting cells, the mesangial cells within the glomerulus, and the 
      pericytes in the retina. The genes and molecular mechanisms predisposing retinal 
      and glomerular pericytes to diabetic injury are poorly characterized. In this 
      study, the genetic deletion of proteasome activator genes, PA28alpha and PA28beta genes, 
      protected the diabetic mice in the experimental STZ-induced diabetes model 
      against renal injury and retinal microvascular injury and prolonged their 
      survival compared with wild type STZ diabetic mice. The improved wellbeing and 
      reduced renal damage was associated with diminished expression of Osteopontin 
      (OPN) and Monocyte Chemoattractant Protein-1 (MCP-1) in the glomeruli of 
      STZ-injected PA28alpha/PA28beta double knockout (Pa28alphabetaDKO) mice and also in cultured 
      mesangial cells and retinal pericytes isolated from Pa28alphabetaDKO mice that were 
      grown in high glucose. The mesangial PA28-mediated expression of OPN under high 
      glucose conditions was suppressed by peptides capable of inhibiting the binding 
      of PA28 to the 20S proteasome. Collectively, our findings demonstrate that 
      diabetic hyperglycemia promotes PA28-mediated alteration of proteasome activity 
      in vulnerable perivascular cells resulting in microvascular injury and 
      development of DN and DR.
FAU - Yadranji Aghdam, Saeed
AU  - Yadranji Aghdam S
AUID- ORCID: 0000-0001-7865-4854
AD  - Reynolds Institute on Aging, Room No. 4151, 629 Jack Stephens Drive, Little Rock, 
      AR 72205, USA; Department of Geriatrics, University of Arkansas for Medical 
      Sciences, Little Rock, AR, USA.
FAU - Mahmoudpour, Ali
AU  - Mahmoudpour A
AD  - Norgen Biotek Corp., 3430 Schmon Parkway, Thorold, ON, Canada L2V 4Y6.
LA  - eng
GR  - P30 EY016665/EY/NEI NIH HHS/United States
GR  - RC4 EY021357/EY/NEI NIH HHS/United States
PT  - Journal Article
DEP - 20161018
PL  - United States
TA  - Int J Nephrol
JT  - International journal of nephrology
JID - 101546753
PMC - PMC5088333
EDAT- 2016/11/11 06:00
MHDA- 2016/11/11 06:01
PMCR- 2016/10/18
CRDT- 2016/11/11 06:00
PHST- 2016/07/11 00:00 [received]
PHST- 2016/08/08 00:00 [revised]
PHST- 2016/09/06 00:00 [accepted]
PHST- 2016/11/11 06:00 [entrez]
PHST- 2016/11/11 06:00 [pubmed]
PHST- 2016/11/11 06:01 [medline]
PHST- 2016/10/18 00:00 [pmc-release]
AID - 10.1155/2016/3846573 [doi]
PST - ppublish
SO  - Int J Nephrol. 2016;2016:3846573. doi: 10.1155/2016/3846573. Epub 2016 Oct 18.