共 41 条
Nkx2.2 Activates the Ghrelin Promoter in Pancreatic Islet Cells
被引:15
作者:

Hill, Jonathon T.
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h-index: 0
机构:
Columbia Univ, Dept Genet & Dev, New York, NY 10032 USA Columbia Univ, Dept Genet & Dev, New York, NY 10032 USA

Chao, Christina S.
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h-index: 0
机构:
Univ Colorado Denver, Dept Biochem & Mol Genet, Aurora, CO 80045 USA Columbia Univ, Dept Genet & Dev, New York, NY 10032 USA

Anderson, Keith R.
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h-index: 0
机构:
Univ Colorado Denver, Dept Biochem & Mol Genet, Aurora, CO 80045 USA Columbia Univ, Dept Genet & Dev, New York, NY 10032 USA

Kaufman, Fernanda
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h-index: 0
机构:
Univ Colorado Denver, Dept Biochem & Mol Genet, Aurora, CO 80045 USA Columbia Univ, Dept Genet & Dev, New York, NY 10032 USA

Johnson, Christopher W.
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h-index: 0
机构:
Univ Colorado Denver, Dept Biochem & Mol Genet, Aurora, CO 80045 USA Columbia Univ, Dept Genet & Dev, New York, NY 10032 USA

Sussel, Lori
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h-index: 0
机构:
Columbia Univ, Dept Genet & Dev, New York, NY 10032 USA Columbia Univ, Dept Genet & Dev, New York, NY 10032 USA
机构:
[1] Columbia Univ, Dept Genet & Dev, New York, NY 10032 USA
[2] Univ Colorado Denver, Dept Biochem & Mol Genet, Aurora, CO 80045 USA
基金:
美国国家卫生研究院;
关键词:
FOOD-INTAKE;
IN-VIVO;
INSULIN-SECRETION;
ACYLATED PEPTIDE;
EPSILON-CELLS;
RAT PANCREAS;
BETA-CELLS;
EXPRESSION;
ENDOCRINE;
MOUSE;
D O I:
10.1210/me.2009-0360
中图分类号:
R5 [内科学];
学科分类号:
1002 ;
100201 ;
摘要:
Nkx2.2 is an essential regulator of pancreatic endocrine differentiation. Nkx2.2-null mice are completely devoid of beta-ells and have a large reduction of alpha- and PP cells. In the place of these islet populations, there is a corresponding increase in the ghrelin-positive epsilon-cells. Molecular studies have indicated that Nkx2.2 functions as an activator and repressor to regulate islet cell fate decisions. To determine whether Nkx2.2 is solely important for islet cell fate decisions or also has the capability to control ghrelin at the promoter level, we studied the transcriptional regulation of the ghrelin promoter within the pancreas, in vitro and in vivo. These studies demonstrate that both of the previously identified transcriptional start sites in the ghrelin promoter are active within the embryonic pancreas; however, the long transcript is preferentially up-regulated in the Nkx2.2-null pancreas. We also show that the promoter region between -619 and -488 bp upstream of the translational start site is necessary for repression of ghrelin in alpha TC1 and beta TC6 cells. Surprisingly, we also show that Nkx2.2 is able to bind to and activate the ghrelin promoter in several cell lines that do or do not express endogenous ghrelin. Together, these results suggest that the up-regulation of ghrelin expression in the Nkx2.2-null mice is not due to loss of repression of the ghrelin promoter in the nonghrelin islet populations. Furthermore, Nkx2.2 may contribute to the activation of ghrelin in mature islet epsilon-cells. ( Molecular Endocrinology 24: 381-390, 2010)
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页码:381 / 390
页数:10
相关论文
共 41 条
[1]
Cooperative Transcriptional Regulation of the Essential Pancreatic Islet Gene NeuroD1 (Beta2) by Nkx2.2 and Neurogenin 3
[J].
Anderson, Keith R.
;
Torres, Ciara A.
;
Solomon, Keely
;
Becker, Thomas C.
;
Newgard, Christopher B.
;
Wright, Christopher V.
;
Hagman, James
;
Sussel, Lori
.
JOURNAL OF BIOLOGICAL CHEMISTRY,
2009, 284 (45)
:31236-31248

Anderson, Keith R.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Colorado, Hlth Sci Ctr, Dept Biochem, Denver, CO 80045 USA
Univ Colorado, Hlth Sci Ctr, Program Mol Biol, Denver, CO 80045 USA Univ Colorado, Hlth Sci Ctr, Dept Biochem, Denver, CO 80045 USA

Torres, Ciara A.
论文数: 0 引用数: 0
h-index: 0
机构:
Columbia Univ, Dept Genet & Dev, New York, NY 10032 USA Univ Colorado, Hlth Sci Ctr, Dept Biochem, Denver, CO 80045 USA

Solomon, Keely
论文数: 0 引用数: 0
h-index: 0
机构:
Vanderbilt Univ, Dept Cell & Dev Biol, Nashville, TN 37232 USA Univ Colorado, Hlth Sci Ctr, Dept Biochem, Denver, CO 80045 USA

Becker, Thomas C.
论文数: 0 引用数: 0
h-index: 0
机构:
Duke Univ, Med Ctr, Sarah W Stedman Nutr & Metab Ctr, Durham, NC 27704 USA
Duke Univ, Med Ctr, Dept Pharmacol, Durham, NC 27704 USA
Duke Univ, Med Ctr, Dept Canc Biol & Med, Durham, NC 27704 USA Univ Colorado, Hlth Sci Ctr, Dept Biochem, Denver, CO 80045 USA

Newgard, Christopher B.
论文数: 0 引用数: 0
h-index: 0
机构:
Duke Univ, Med Ctr, Sarah W Stedman Nutr & Metab Ctr, Durham, NC 27704 USA
Duke Univ, Med Ctr, Dept Pharmacol, Durham, NC 27704 USA
Duke Univ, Med Ctr, Dept Canc Biol & Med, Durham, NC 27704 USA Univ Colorado, Hlth Sci Ctr, Dept Biochem, Denver, CO 80045 USA

Wright, Christopher V.
论文数: 0 引用数: 0
h-index: 0
机构:
Vanderbilt Univ, Dept Cell & Dev Biol, Nashville, TN 37232 USA Univ Colorado, Hlth Sci Ctr, Dept Biochem, Denver, CO 80045 USA

Hagman, James
论文数: 0 引用数: 0
h-index: 0
机构:
Natl Jewish Hlth Ctr, Integrated Dept Immunol, Denver, CO 80206 USA Univ Colorado, Hlth Sci Ctr, Dept Biochem, Denver, CO 80045 USA

Sussel, Lori
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Colorado, Hlth Sci Ctr, Dept Biochem, Denver, CO 80045 USA
Columbia Univ, Dept Genet & Dev, New York, NY 10032 USA Univ Colorado, Hlth Sci Ctr, Dept Biochem, Denver, CO 80045 USA
[2]
Ghrelin-producing epsilon cells in the developing and adult human pancreas
[J].
Andralojc, K. M.
;
Mercalli, A.
;
Nowak, K. W.
;
Albarello, L.
;
Calcagno, R.
;
Luzi, L.
;
Bonifacio, E.
;
Doglioni, C.
;
Piemonti, L.
.
DIABETOLOGIA,
2009, 52 (03)
:486-493

Andralojc, K. M.
论文数: 0 引用数: 0
h-index: 0
机构:
Poznan Univ Life Sci, Dept Anim Physiol & Biochem, Poznan, Poland Ist Sci San Raffaele, Diabet Res Inst HSR DRI, I-20132 Milan, Italy

Mercalli, A.
论文数: 0 引用数: 0
h-index: 0
机构:
Ist Sci San Raffaele, Diabet Res Inst HSR DRI, I-20132 Milan, Italy Ist Sci San Raffaele, Diabet Res Inst HSR DRI, I-20132 Milan, Italy

Nowak, K. W.
论文数: 0 引用数: 0
h-index: 0
机构:
Poznan Univ Life Sci, Dept Anim Physiol & Biochem, Poznan, Poland Ist Sci San Raffaele, Diabet Res Inst HSR DRI, I-20132 Milan, Italy

Albarello, L.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Vita Salute San Raffaele, Dept Human Pathol, Milan, Italy Ist Sci San Raffaele, Diabet Res Inst HSR DRI, I-20132 Milan, Italy

Calcagno, R.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Vita Salute San Raffaele, Dept Human Pathol, Milan, Italy Ist Sci San Raffaele, Diabet Res Inst HSR DRI, I-20132 Milan, Italy

Luzi, L.
论文数: 0 引用数: 0
h-index: 0
机构:
Ist Sci San Raffaele, Dept Med, Unit Nutr & Metab, I-20132 Milan, Italy
Univ Milan, Phys Exercise Hlth & Wellness Ctr, Milan, Italy Ist Sci San Raffaele, Diabet Res Inst HSR DRI, I-20132 Milan, Italy

Bonifacio, E.
论文数: 0 引用数: 0
h-index: 0
机构:
Tech Univ Dresden, Ctr Regenerat Therapies Dresden, D-8027 Dresden, Germany Ist Sci San Raffaele, Diabet Res Inst HSR DRI, I-20132 Milan, Italy

Doglioni, C.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Vita Salute San Raffaele, Dept Human Pathol, Milan, Italy Ist Sci San Raffaele, Diabet Res Inst HSR DRI, I-20132 Milan, Italy

Piemonti, L.
论文数: 0 引用数: 0
h-index: 0
机构:
Ist Sci San Raffaele, Diabet Res Inst HSR DRI, I-20132 Milan, Italy Ist Sci San Raffaele, Diabet Res Inst HSR DRI, I-20132 Milan, Italy
[3]
PROGASTRIN EXPRESSION IN MAMMALIAN PANCREAS
[J].
BARDRAM, L
;
HILSTED, L
;
REHFELD, JF
.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,
1990, 87 (01)
:298-302

BARDRAM, L
论文数: 0 引用数: 0
h-index: 0
机构: UNIV COPENHAGEN,RIGSHOSP,DEPT SURG GASTROENTEROL,DK-2100 COPENHAGEN,DENMARK

HILSTED, L
论文数: 0 引用数: 0
h-index: 0
机构: UNIV COPENHAGEN,RIGSHOSP,DEPT SURG GASTROENTEROL,DK-2100 COPENHAGEN,DENMARK

REHFELD, JF
论文数: 0 引用数: 0
h-index: 0
机构: UNIV COPENHAGEN,RIGSHOSP,DEPT SURG GASTROENTEROL,DK-2100 COPENHAGEN,DENMARK
[4]
Ghrelin inhibits the proliferative activity of immature Leydig cells in vivo and regulates stem cell factor messenger ribonucleic acid expression in rat testis
[J].
Barreiro, ML
;
Gaytan, F
;
Castellano, JM
;
Suominen, JS
;
Roa, J
;
Gaytan, M
;
Aguilar, E
;
Dieguez, C
;
Toppari, J
;
Tena-Sempere, M
.
ENDOCRINOLOGY,
2004, 145 (11)
:4825-4834

Barreiro, ML
论文数: 0 引用数: 0
h-index: 0
机构: Univ Cordoba, Fac Med, Dept Cell Biol Physiol & Immunol, E-14004 Cordoba, Spain

Gaytan, F
论文数: 0 引用数: 0
h-index: 0
机构: Univ Cordoba, Fac Med, Dept Cell Biol Physiol & Immunol, E-14004 Cordoba, Spain

Castellano, JM
论文数: 0 引用数: 0
h-index: 0
机构: Univ Cordoba, Fac Med, Dept Cell Biol Physiol & Immunol, E-14004 Cordoba, Spain

Suominen, JS
论文数: 0 引用数: 0
h-index: 0
机构: Univ Cordoba, Fac Med, Dept Cell Biol Physiol & Immunol, E-14004 Cordoba, Spain

Roa, J
论文数: 0 引用数: 0
h-index: 0
机构: Univ Cordoba, Fac Med, Dept Cell Biol Physiol & Immunol, E-14004 Cordoba, Spain

Gaytan, M
论文数: 0 引用数: 0
h-index: 0
机构: Univ Cordoba, Fac Med, Dept Cell Biol Physiol & Immunol, E-14004 Cordoba, Spain

Aguilar, E
论文数: 0 引用数: 0
h-index: 0
机构: Univ Cordoba, Fac Med, Dept Cell Biol Physiol & Immunol, E-14004 Cordoba, Spain

Dieguez, C
论文数: 0 引用数: 0
h-index: 0
机构: Univ Cordoba, Fac Med, Dept Cell Biol Physiol & Immunol, E-14004 Cordoba, Spain

论文数: 引用数:
h-index:
机构:

Tena-Sempere, M
论文数: 0 引用数: 0
h-index: 0
机构: Univ Cordoba, Fac Med, Dept Cell Biol Physiol & Immunol, E-14004 Cordoba, Spain
[5]
Cellular location and hormonal regulation of ghrelin expression in rat testis
[J].
Barreiro, ML
;
Gaytán, F
;
Caminos, JE
;
Pinilla, L
;
Casanueva, FF
;
Aguilar, E
;
Diéguez, C
;
Tena-Sempere, M
.
BIOLOGY OF REPRODUCTION,
2002, 67 (06)
:1768-1776

Barreiro, ML
论文数: 0 引用数: 0
h-index: 0
机构: Univ Cordoba, Fac Med, Physiol Sect, Dept Cell Biol Physiol & Immunol, Cordoba 14004, Spain

Gaytán, F
论文数: 0 引用数: 0
h-index: 0
机构: Univ Cordoba, Fac Med, Physiol Sect, Dept Cell Biol Physiol & Immunol, Cordoba 14004, Spain

Caminos, JE
论文数: 0 引用数: 0
h-index: 0
机构: Univ Cordoba, Fac Med, Physiol Sect, Dept Cell Biol Physiol & Immunol, Cordoba 14004, Spain

Pinilla, L
论文数: 0 引用数: 0
h-index: 0
机构: Univ Cordoba, Fac Med, Physiol Sect, Dept Cell Biol Physiol & Immunol, Cordoba 14004, Spain

Casanueva, FF
论文数: 0 引用数: 0
h-index: 0
机构: Univ Cordoba, Fac Med, Physiol Sect, Dept Cell Biol Physiol & Immunol, Cordoba 14004, Spain

Aguilar, E
论文数: 0 引用数: 0
h-index: 0
机构: Univ Cordoba, Fac Med, Physiol Sect, Dept Cell Biol Physiol & Immunol, Cordoba 14004, Spain

Diéguez, C
论文数: 0 引用数: 0
h-index: 0
机构: Univ Cordoba, Fac Med, Physiol Sect, Dept Cell Biol Physiol & Immunol, Cordoba 14004, Spain

Tena-Sempere, M
论文数: 0 引用数: 0
h-index: 0
机构: Univ Cordoba, Fac Med, Physiol Sect, Dept Cell Biol Physiol & Immunol, Cordoba 14004, Spain
[6]
Body window-enabled in vivo multicolor imaging of transplanted mouse islets expressing an insulin-timer fusion protein
[J].
Bertera, S
;
Geng, XH
;
Tawadrous, Z
;
Bottino, R
;
Balamurugan, AN
;
Rudert, WA
;
Drain, P
;
Watkins, SC
;
Trucco, M
.
BIOTECHNIQUES,
2003, 35 (04)
:718-+

论文数: 引用数:
h-index:
机构:

Geng, XH
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Pittsburgh, Pittsburgh, PA USA Univ Pittsburgh, Pittsburgh, PA USA

Tawadrous, Z
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Pittsburgh, Pittsburgh, PA USA Univ Pittsburgh, Pittsburgh, PA USA

Bottino, R
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Pittsburgh, Pittsburgh, PA USA Univ Pittsburgh, Pittsburgh, PA USA

Balamurugan, AN
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Pittsburgh, Pittsburgh, PA USA Univ Pittsburgh, Pittsburgh, PA USA

Rudert, WA
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Pittsburgh, Pittsburgh, PA USA Univ Pittsburgh, Pittsburgh, PA USA

Drain, P
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Pittsburgh, Pittsburgh, PA USA Univ Pittsburgh, Pittsburgh, PA USA

Watkins, SC
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Pittsburgh, Pittsburgh, PA USA Univ Pittsburgh, Pittsburgh, PA USA

Trucco, M
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Pittsburgh, Pittsburgh, PA USA Univ Pittsburgh, Pittsburgh, PA USA
[7]
Ghrelin gene expression is markedly higher in fetal pancreas compared with fetal stomach: Effect of maternal fasting
[J].
Chanoine, JP
;
Wong, ACK
.
ENDOCRINOLOGY,
2004, 145 (08)
:3813-3820

Chanoine, JP
论文数: 0 引用数: 0
h-index: 0
机构:
Univ British Columbia, British Columbia Childrens Hosp, Endocrinol & Diabet Unit, Vancouver, BC V6H 3V4, Canada Univ British Columbia, British Columbia Childrens Hosp, Endocrinol & Diabet Unit, Vancouver, BC V6H 3V4, Canada

Wong, ACK
论文数: 0 引用数: 0
h-index: 0
机构:
Univ British Columbia, British Columbia Childrens Hosp, Endocrinol & Diabet Unit, Vancouver, BC V6H 3V4, Canada Univ British Columbia, British Columbia Childrens Hosp, Endocrinol & Diabet Unit, Vancouver, BC V6H 3V4, Canada
[8]
Genetic identification of a novel NeuroDl function in the early differentiation of islet α, PP and ε cells
[J].
Chao, Christina S.
;
Loomis, Zoe L.
;
Lee, Jacqueline E.
;
Sussel, Lori
.
DEVELOPMENTAL BIOLOGY,
2007, 312 (02)
:523-532

Chao, Christina S.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Colorado, Ctr Hlth Sci, Dept Biochem & Mol Genet, Aurora, CO 80045 USA
Univ Colorado, Ctr Hlth Sci, Med Sci Training Program, Cell & Dev Biol Program, Aurora, CO 80045 USA Univ Colorado, Ctr Hlth Sci, Dept Biochem & Mol Genet, Aurora, CO 80045 USA

Loomis, Zoe L.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Colorado, Ctr Hlth Sci, Dept Biochem & Mol Genet, Aurora, CO 80045 USA Univ Colorado, Ctr Hlth Sci, Dept Biochem & Mol Genet, Aurora, CO 80045 USA

Lee, Jacqueline E.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA Univ Colorado, Ctr Hlth Sci, Dept Biochem & Mol Genet, Aurora, CO 80045 USA

Sussel, Lori
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Colorado, Ctr Hlth Sci, Dept Biochem & Mol Genet, Aurora, CO 80045 USA Univ Colorado, Ctr Hlth Sci, Dept Biochem & Mol Genet, Aurora, CO 80045 USA
[9]
Transcription factor occupancy of the insulin gene in vivo -: Evidence for direct regulation by Nkx2.2
[J].
Cissell, MA
;
Zhao, L
;
Sussel, L
;
Henderson, E
;
Stein, R
.
JOURNAL OF BIOLOGICAL CHEMISTRY,
2003, 278 (02)
:751-756

Cissell, MA
论文数: 0 引用数: 0
h-index: 0
机构: Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA

Zhao, L
论文数: 0 引用数: 0
h-index: 0
机构: Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA

Sussel, L
论文数: 0 引用数: 0
h-index: 0
机构: Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA

Henderson, E
论文数: 0 引用数: 0
h-index: 0
机构: Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA

Stein, R
论文数: 0 引用数: 0
h-index: 0
机构: Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA
[10]
Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans
[J].
Date, Y
;
Kojima, M
;
Hosoda, H
;
Sawaguchi, A
;
Mondal, MS
;
Suganuma, T
;
Matsukura, S
;
Kangawa, K
;
Nakazato, M
.
ENDOCRINOLOGY,
2000, 141 (11)
:4255-4261

Date, Y
论文数: 0 引用数: 0
h-index: 0
机构: Miyazaki Med Coll, Dept Internal Med, Div 3, Kiyotake, Miyazaki 8891692, Japan

Kojima, M
论文数: 0 引用数: 0
h-index: 0
机构: Miyazaki Med Coll, Dept Internal Med, Div 3, Kiyotake, Miyazaki 8891692, Japan

Hosoda, H
论文数: 0 引用数: 0
h-index: 0
机构: Miyazaki Med Coll, Dept Internal Med, Div 3, Kiyotake, Miyazaki 8891692, Japan

Sawaguchi, A
论文数: 0 引用数: 0
h-index: 0
机构: Miyazaki Med Coll, Dept Internal Med, Div 3, Kiyotake, Miyazaki 8891692, Japan

Mondal, MS
论文数: 0 引用数: 0
h-index: 0
机构: Miyazaki Med Coll, Dept Internal Med, Div 3, Kiyotake, Miyazaki 8891692, Japan

Suganuma, T
论文数: 0 引用数: 0
h-index: 0
机构: Miyazaki Med Coll, Dept Internal Med, Div 3, Kiyotake, Miyazaki 8891692, Japan

Matsukura, S
论文数: 0 引用数: 0
h-index: 0
机构: Miyazaki Med Coll, Dept Internal Med, Div 3, Kiyotake, Miyazaki 8891692, Japan

Kangawa, K
论文数: 0 引用数: 0
h-index: 0
机构: Miyazaki Med Coll, Dept Internal Med, Div 3, Kiyotake, Miyazaki 8891692, Japan

Nakazato, M
论文数: 0 引用数: 0
h-index: 0
机构: Miyazaki Med Coll, Dept Internal Med, Div 3, Kiyotake, Miyazaki 8891692, Japan