PMID- 29053707
OWN - NLM
STAT- MEDLINE
DCOM- 20171121
LR  - 20220409
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 10
DP  - 2017
TI  - High glucose augments angiotensinogen in human renal proximal tubular cells 
      through hepatocyte nuclear factor-5.
PG  - e0185600
LID - 10.1371/journal.pone.0185600 [doi]
LID - e0185600
AB  - High glucose has been demonstrated to induce angiotensinogen (AGT) synthesis in 
      the renal proximal tubular cells (RPTCs) of rats, which may further activate the 
      intrarenal renin-angiotensin system (RAS) and contribute to diabetic nephropathy. 
      This study aimed to investigate the effects of high glucose on AGT in the RPTCs 
      of human origin and identify the glucose-responsive transcriptional factor(s) 
      that bind(s) to the DNA sequences of AGT promoter in human RPTCs. Human kidney 
      (HK)-2 cells were treated with normal glucose (5.5 mM) and high glucose (15.0 
      mM), respectively. Levels of AGT mRNA and AGT secretion of HK-2 cells were 
      measured by real-time polymerase chain reaction (PCR) and enzyme-linked 
      immunosorbent assay (ELISA), respectively. Consecutive 5'-end deletion mutant 
      constructs and different site-directed mutagenesis products of human AGT promoter 
      sequences were respectively transfected into HK-2 cells, followed by AGT promoter 
      activity measurement through dual luciferase assay. High glucose significantly 
      augmented the levels of AGT mRNA and AGT secretion of HK-2 cells, compared with 
      normal glucose treatment. High glucose also significantly augmented AGT promoter 
      activity in HK-2 cells transfected with the constructs of human AGT promoter 
      sequences, compared with normal glucose treatment. Hepatocyte nuclear factor 
      (HNF)-5 was found to be one of the glucose-responsive transcriptional factors of 
      AGT in human RPTCs, since the mutation of its binding sites within AGT promoter 
      sequences abolished the above effects of high glucose on AGT promoter activity as 
      well as levels of AGT mRNA and its secretion. The present study has demonstrated, 
      for the first time, that high glucose augments AGT in human RPTCs through HNF-5, 
      which provides a potential therapeutic target for diabetic nephropathy.
FAU - Wang, Juan
AU  - Wang J
AD  - Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, 
      Japan.
AD  - Department of Immuno-oncology, Fourth Hospital of Hebei Medical University, 
      Shijiazhuang, P.R. China.
FAU - Shibayama, Yuki
AU  - Shibayama Y
AD  - Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, 
      Japan.
FAU - Kobori, Hiroyuki
AU  - Kobori H
AD  - Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, 
      Japan.
AD  - Departments of Pharmacology and of Nephrology, School of Medicine, International 
      University of Health and Welfare, Tokyo, Japan.
FAU - Liu, Ya
AU  - Liu Y
AD  - Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, 
      Japan.
FAU - Kobara, Hideki
AU  - Kobara H
AD  - Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa 
      University, Kagawa, Japan.
FAU - Masaki, Tsutomu
AU  - Masaki T
AD  - Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa 
      University, Kagawa, Japan.
FAU - Wang, Zhiyu
AU  - Wang Z
AD  - Department of Immuno-oncology, Fourth Hospital of Hebei Medical University, 
      Shijiazhuang, P.R. China.
FAU - Nishiyama, Akira
AU  - Nishiyama A
AUID- ORCID: 0000-0001-5971-820X
AD  - Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, 
      Japan.
LA  - eng
PT  - Journal Article
DEP - 20171020
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (FOXM1 protein, human)
RN  - 0 (Forkhead Box Protein M1)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
RN  - 11002-13-4 (Angiotensinogen)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Angiotensinogen/genetics/*metabolism
MH  - Animals
MH  - Cell Line
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Forkhead Box Protein M1/*metabolism
MH  - Glucose/*administration & dosage/pharmacology
MH  - Humans
MH  - Kidney Tubules, Proximal/*drug effects/metabolism
MH  - Promoter Regions, Genetic
MH  - RNA, Messenger/genetics
MH  - Rats
MH  - Transcription Factors/metabolism
PMC - PMC5650141
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2017/10/21 06:00
MHDA- 2017/11/29 06:00
PMCR- 2017/10/20
CRDT- 2017/10/21 06:00
PHST- 2017/03/13 00:00 [received]
PHST- 2017/09/17 00:00 [accepted]
PHST- 2017/10/21 06:00 [entrez]
PHST- 2017/10/21 06:00 [pubmed]
PHST- 2017/11/29 06:00 [medline]
PHST- 2017/10/20 00:00 [pmc-release]
AID - PONE-D-17-09947 [pii]
AID - 10.1371/journal.pone.0185600 [doi]
PST - epublish
SO  - PLoS One. 2017 Oct 20;12(10):e0185600. doi: 10.1371/journal.pone.0185600. 
      eCollection 2017.