Yamaguchi University Navigator for Open access Collection and Archives

博士(医学)山口大学Yamaguchi Universit

瀬戸, 哲也

Methylglyoxal MG
MG
Osteocalcin Bone sialoprotein
MG
in vitro MG
MG Osterix
Runx2
Osteocalcin
Osteocalcin MG
MG
MG MG



Romanian

Methylglyoxalは,骨芽細胞の終末分化を抑制することにより，仮骨の石灰化を抑制し，骨折治癒を障害する

緒方, 惟彦

HIF- dependent regulation of angiogenic factor expression 
in Müller cells by mechanical stimulation
HIF-1
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2 
1.
(VEGF)
mRNA VEGF
-1 (HIF-1 ) mRNA 1(ANG1)
VEGF HIF-1 CAY10585
RNA (RNA-seq)
HIF-
1  VEGF HIF-1
3 
2.
[1, 2]
[3-5]
Ca2+ c-Fos
[6]
[7-10] Yap
Src [11-14]
VEGF
[15, 16]
VEGF
[17-19] VEGF
Yap øTRP÷
HIF- [20-23] HIF-
[24] VEGF-A
[25]
VEGF ANG1
HIF-
HIF-
3.
in vitro
4 
4.
1)
(MIO-M1) ( )
10 cm 10% (Gibco) 1%
(Gibco) 2mM L- (Gibco) (D6429
Sigma-Aldrich) 37 5% CO2
MIO-M1 I (IAC-50 Koken)
(SC-0044 SC-0040 Strex)
HIF-1 CAY10585(Abcam)
2 CAY10585 10 uM
HIF-1 HIF-1 [23 26]
CAY10585 (STB-1400 Strex) 24
0 10% 0.5 Hz
37 5% CO2 3
MIO-M1 150mM NaCl 5mM MgCl2 100mM NaF 100 
 Na3VO4 1mM EGTA 1mM EDTA 0.25% SDS 0.25% C24H39NaO4 1% Nonidet P-40
(Nacalai Tesque)
11,000 g 4°C 10 Pierce BCA
(23227 Thermo Fisher Scientific) 5-20% e-PAGEL
(Atto) 20mA 80 SDS
0.45 m  (Cytiva) 5%
0.1% Tween-20 (TBS-T) 4
1 HIF-1
(ab51608 Abcam) - (TG074 Sigma-
Aldrich) 4 TBS-T (NA9340U Sigma-
Aldrich) (NA9310V Sigma-Aldrich) 
1 (Chemi-Lumi One Super Nacalai Tesque
PRN2235 Cytiva) ChemiDoc Imaging System(Bio-Rad)
Image J
HIF-1 -
5 
(ELISA)
MIO-M1 VEGF ELISA(DVE00 R&D System)
VEGF Multiskan FC Manager
(Thermo Fisher Scientific) VEGF VEGF
(RT-qPCR) 
MIO-M1 Sepasol RNA Super G(09379-55 Nacalai Tesque) RNA
RNA 260/280 nm NanoDrop Lite (Thermo Fisher 
Scientific) 1.8 2.0
RNA ReverTra Ace qPCR RT Master Mix with gDNA Remover(FSQ-301 Toyobo)
cDNA cDNA Taq Pro Universal SYBR qPCR Master 
Mix(Q712-02 Vazyme Biotech) StepOnePlus (Thermo Fisher Scientific)
(qPCR) qPCR
VEGF-A(hVEGF-A 1958402) 5'-
GCAGAATCATCACGAAGTGGT-3' 5'-ACCAACGTACACGCTCCAG-3' ANG1(hANG1
1669549) 5'-AGCGCCGAAGTCCAGAAAAC-3' 5'-TACTCTCACGACAGTTGCCAT-3'
PIGF(hPIGF 1997001) 5'-TGACATGGTTGTGCATCTGTT-3' 5'- 
ACTCTATCAGTGGTGCTCCATAC-3' HIF-1 (hHIF1 1718012) 5'- 
GAACGTCGAAAAGAAAAGTCTCG-3' 5 -CCTTATCAAGATGCGAACTCACA-3
GAPDH(hGAPDH 1955533) 5'-CTGGGCTACACTGAGCACC-3 5 -
AAGTGGTCGTTGAGGGCAATG-3' VEGF-A ANG1 PIGF HIF-1 mRNA
CT -3-
(GAPDH)mRNA
RNA (RNA-seq) 
Maxwell RSC Simply RNA Cell Kit(AS1390 Promega) RNA
NanoDrop One (Thermo Fisher Scientific) Tapestation 4200 High Sensitivity 
RNA (#5067-5579 Agilent Technologies) RINe (RNA Integrity Number )
NEBNext Ultra  RNA Library Prep 
Kit for Illumina(E7770 New England BioLabs)  RNA-seq
200nt RNA cDNA
AMPure XP c1000 Touch 
Thermal Cycler(Bio-Rad) PCR NEBNext Multiplex Oligos for 
Illumina(E6446 New England BioLabs)
AMPure XP Qubit 2.0 Fluorometer(Thermo Fisher 
Scientific) Tapestation 4200 D1000 (#5067-5582
Agilent Technologies) 50 bp cDNA NovaSeq 
6000 S1 Reagent Kit V1.5(20028317 Illumina) CLC Genomics 
6 
Workbench(GWB)22.0.1(Qiage) Illumina NovaSeq 6000
BCL bcl2fastq v2.20.0.402 fastq
fastq GWB GWB Trim reads 2.6
3' 1 bp
GWB RNA-Seq 
Analysis 2.6
TPM 2 Yes
Human GRCh37(hg19) release-75 GWB
Ensembl
 TPM 1 log2  JMP Pro 15 
Metascape 
 GO( ) KEGG( )
(P < 0.05  < 0.01)
0.3 
2)
+SEM t
P 0.05
5.
MIO-M1 VEGF
[27]
MIO-M1 12 24
RT-qPCR 24 MIO-M1
VEGF-A mRNA ( 1a)
ANG1 mRNA[28] ( 1a) (PlGF)
( 1a)  ELISA 24
MIO-M1 VEGF 2 (  1b)
MIO-M1 HIF-1
VEGF-A HIF-1
[29] MIO-M1 HIF-1 mRNA
RT-qPCR 24 
MIO-M1 HIF-1 mRNA (  2a)  HIF-1
(  2b)
7 
MIO-M1 HIF1- VEGF-A ANG1
HIF-1 MIO-M1 VEGF-A
HIF-1 CAY10585 MIO-M1
RT-qPCR 24 MIO-M1
VEGF-A mRNA CAY10585 ( 3) ANG1 
mRNA CAY10585 ( 3) PlGF mRNA
CAY10585 ( 3)
HIF-1  mRNA
( 3)
MIO-M1 HIF1- VEGF
MIO-M1 VEGF-A HIF-1
CAY10585 MIO-M1
ELISA 24
MIO-M1 HIF-1 CAY10585
( 4a)  ELISA 24
VEGF CAY10585
4b
MIO-M1 
24  MIO-M1  RNA-seq 
2 P  <0.05 
Metascape GO KEGG
( 5a)
DNA 
( 5b)
6.
in vitro
HIF-1
VEGF ANG1
RNA-seq
Epha2 Nrn1
[30] HIF-1 VEGF
8 
[31 32] HIF-
1 VEGF
HIF-1
[33-35] HIF-1 HIF-
1 2 p300/CBP [36]
VEGF
(HRE) [37]
NF- B HIF-1 [38]
NF- B HIF-1
[39] VEGF
HIF-1 HIF-1 CAY10585
VEGF
HIF-1
VEGF HIF-1 24
ANG1
[39-42] ANG1 
ANG1 CAY10585 
HIF-1 ANG1
HIF-1 ANG1
[43-45] HIF-1 HRE (rHRE)
[46] ANG1
2 HRE [47] ANG1 
HRE HIF-1 HIF-2
[48] HIF-1 HIF-2 1 HIF-2
HIF-1 [48]
ANG1 HIF-2
HIF-2 mRNA
RNA-seq
AMD VEGF
[49 50]
[51-54]
 [55] VEGF
[15 23]
9 
[1 2]
HIF-1 VEGF ANG1
CAY10585 HIF-1
VEGF [56] HIF-1
VEGF CAY10585
[26] FOXO3a [57]
-6 [58]
CAY10585 ANG1
HIF-1 VEGF
7.
HIF-1
HIF-1
8.
, 
, 
, , 
9.
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15
MIO-M1 (a) 
MIO-M1 VEGF-A ANG1 PIGF mRNA RT-qPCR
GAPDH mRNA (b)MIO-M1
VEGF ELISA (N=3)
*P < 0.05 **P < 0.01 0 (Student t )
MIO-M1 HIF- (a)
MIO-M1 HIF- RT-qPCR GAPDH
mRNA (b) MIO-M1
HIF- -
(N=3) **P < 0.01 0 (Student 
t )
1
2
16
3
MIO-M1 HIF- VEGF-A ANG1 PIGF
HIF- HIF-
MIO-M1 VEGF-A ANG1 PIGF HIF- RT-qPCR
GAPDH mRNA (N=3) n.s. 
*P < 0.05 **P < 0.01 0 (Student t )
MIO-M1 HIF- VEGF (a)
HIF- MIO-M1 HIF-
-
(b)(a) VEGF ELISA
(N=3) n.s. **P < 0.01 0 (Student 
t )
4
17
MIO-M1 (a)
0 24 MIO-M1 RNA-seq
P < 0.05 Metascape
3
(b)(a)
5


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