PMID- 21526116
OWN - NLM
STAT- MEDLINE
DCOM- 20110816
LR  - 20240313
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 6
IP  - 4
DP  - 2011 Apr 22
TI  - Functional characterization of the plasmacytoma variant translocation 1 gene 
      (PVT1) in diabetic nephropathy.
PG  - e18671
LID - 10.1371/journal.pone.0018671 [doi]
LID - e18671
AB  - We previously observed association between variants in the plasmacytoma variant 
      translocation 1 gene (PVT1) and end-stage renal disease (ESRD) attributed to both 
      type 1 and type 2 diabetes, and demonstrated PVT1 expression in a variety of 
      renal cell types. While these findings suggest a role for PVT1 in the development 
      of ESRD, potential mechanisms for involvement remain unknown. The goal of this 
      study was to identify possible molecular mechanisms by which PVT1 may contribute 
      to the development and progression of diabetic kidney disease. We knocked-down 
      PVT1 expression in mesangial cells using RNA interference, and analyzed RNA and 
      protein levels of fibronectin 1 (FN1), collagen, type IV, alpha 1 (COL4A1), 
      transforming growth factor beta 1 (TGFB1) and plasminogen activator inhibitor-1 
      (SERPINE1 or PAI-1) by qPCR and ELISA, respectively. PVT1 expression was 
      significantly upregulated by glucose treatment in human mesangial cells, as were 
      levels of FN1, COL4A1, TGFB1, and PAI-1. Importantly, PVT1 knockdown 
      significantly reduced mRNA and protein levels of the major ECM proteins, FN1 and 
      COL4A1, and two key regulators of ECM proteins, TGFB1 and PAI-1. However, we 
      observed a higher and more rapid reduction in levels of secreted FN1, COL4A1, and 
      PAI-1 compared with TGFB1, suggesting that at least some of the PVT1 effects on 
      ECM proteins may be independent of this cytokine. These results indicate that 
      PVT1 may mediate the development and progression of diabetic nephropathy through 
      mechanisms involving ECM accumulation.
FAU - Alvarez, M Lucrecia
AU  - Alvarez ML
AD  - Diabetes, Cardiovascular and Metabolic Diseases Center, Translational Genomics 
      Research Institute, Phoenix, Arizona, United States of America.
FAU - DiStefano, Johanna K
AU  - DiStefano JK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110422
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Extracellular Matrix Proteins)
RN  - 0 (PVT1 long-non-coding RNA, human)
RN  - 0 (Plasminogen Activator Inhibitor 1)
RN  - 0 (Proteins)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transforming Growth Factor beta1)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Diabetic Nephropathies/*genetics
MH  - Extracellular Matrix/drug effects/metabolism
MH  - Extracellular Matrix Proteins/genetics/metabolism
MH  - Gene Expression Regulation/drug effects
MH  - Gene Knockdown Techniques
MH  - Glucose/pharmacology
MH  - Humans
MH  - Mesangial Cells/drug effects/metabolism/pathology
MH  - Models, Biological
MH  - Plasminogen Activator Inhibitor 1/genetics/metabolism
MH  - Proteins/*genetics/metabolism
MH  - RNA, Long Noncoding
MH  - RNA, Messenger/genetics/metabolism
MH  - Transforming Growth Factor beta1/genetics/metabolism
PMC - PMC3081298
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2011/04/29 06:00
MHDA- 2011/08/17 06:00
PMCR- 2011/04/22
CRDT- 2011/04/29 06:00
PHST- 2010/10/15 00:00 [received]
PHST- 2011/03/14 00:00 [accepted]
PHST- 2011/04/29 06:00 [entrez]
PHST- 2011/04/29 06:00 [pubmed]
PHST- 2011/08/17 06:00 [medline]
PHST- 2011/04/22 00:00 [pmc-release]
AID - PONE-D-10-03544 [pii]
AID - 10.1371/journal.pone.0018671 [doi]
PST - epublish
SO  - PLoS One. 2011 Apr 22;6(4):e18671. doi: 10.1371/journal.pone.0018671.