Characterization of growth-differentiation factor 15, a transforming growth factor β superfamily member induced following liver injury

Edward C. Hsiao, Leonidas G. Koniaris, Teresa Zimmers-Koniaris, Suzanne M. Sebald, Thanh V. Huynh, Se Jin Lee

Research output: Contribution to journalArticle

Abstract

We have identified a new murine transforming growth factor β superfamily member, growth-differentiation factor 15 (Gdf15), that is expressed at highest levels in adult liver. As determined by Northern analysis, the expression of Gdf15 in liver was rapidly and dramatically up- regulated following various surgical and chemical treatments that cause acute liver injury and regeneration. In situ hybridization analysis revealed distinct patterns of Gdf15 mRNA localization that appeared to reflect the known patterns of hepatocyte injury in each experimental treatment. In addition, treatment of two hepatocyte-like cell lines with either carbon tetrachloride or heat shock induced Gdf15 mRNA expression, indicating that direct cellular injury can induce Gdf15 expression in the absence of other cell types, such as inflammatory cells. In order to investigate the potential functions of Gdf15, we created Gdf15 null mice by gene targeting. Homozygous null mice were viable and fertile. Despite the dramatic regulation of Gdf15 expression observed in the partial-hepatectomy and carbon tetrachloride injury models, we found no differences in the injury responses between homozygous null mutants and wild-type mice. Our findings suggest either that Gdf15 does not have a regulatory role in liver injury and regeneration or that Gdf15 function within the liver is redundant with that of other signaling molecules.

Original languageEnglish (US)
Pages (from-to)3742-3751
Number of pages10
JournalMolecular and Cellular Biology
Volume20
Issue number10
DOIs
StatePublished - May 2000

Fingerprint

Growth Differentiation Factor 15
Transforming Growth Factors
Liver
Wounds and Injuries
Liver Regeneration
Carbon Tetrachloride
Hepatocytes
Messenger RNA
Gene Targeting
Hepatectomy
In Situ Hybridization
Shock

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Characterization of growth-differentiation factor 15, a transforming growth factor β superfamily member induced following liver injury. / Hsiao, Edward C.; Koniaris, Leonidas G.; Zimmers-Koniaris, Teresa; Sebald, Suzanne M.; Huynh, Thanh V.; Lee, Se Jin.

In: Molecular and Cellular Biology, Vol. 20, No. 10, 05.2000, p. 3742-3751.

Research output: Contribution to journalArticle

Hsiao, Edward C. ; Koniaris, Leonidas G. ; Zimmers-Koniaris, Teresa ; Sebald, Suzanne M. ; Huynh, Thanh V. ; Lee, Se Jin. / Characterization of growth-differentiation factor 15, a transforming growth factor β superfamily member induced following liver injury. In: Molecular and Cellular Biology. 2000 ; Vol. 20, No. 10. pp. 3742-3751.
@article{891cb6d8fa0e4b20b7435d87b4742e0e,
title = "Characterization of growth-differentiation factor 15, a transforming growth factor β superfamily member induced following liver injury",
abstract = "We have identified a new murine transforming growth factor β superfamily member, growth-differentiation factor 15 (Gdf15), that is expressed at highest levels in adult liver. As determined by Northern analysis, the expression of Gdf15 in liver was rapidly and dramatically up- regulated following various surgical and chemical treatments that cause acute liver injury and regeneration. In situ hybridization analysis revealed distinct patterns of Gdf15 mRNA localization that appeared to reflect the known patterns of hepatocyte injury in each experimental treatment. In addition, treatment of two hepatocyte-like cell lines with either carbon tetrachloride or heat shock induced Gdf15 mRNA expression, indicating that direct cellular injury can induce Gdf15 expression in the absence of other cell types, such as inflammatory cells. In order to investigate the potential functions of Gdf15, we created Gdf15 null mice by gene targeting. Homozygous null mice were viable and fertile. Despite the dramatic regulation of Gdf15 expression observed in the partial-hepatectomy and carbon tetrachloride injury models, we found no differences in the injury responses between homozygous null mutants and wild-type mice. Our findings suggest either that Gdf15 does not have a regulatory role in liver injury and regeneration or that Gdf15 function within the liver is redundant with that of other signaling molecules.",
author = "Hsiao, {Edward C.} and Koniaris, {Leonidas G.} and Teresa Zimmers-Koniaris and Sebald, {Suzanne M.} and Huynh, {Thanh V.} and Lee, {Se Jin}",
year = "2000",
month = "5",
doi = "10.1128/MCB.20.10.3742-3751.2000",
language = "English (US)",
volume = "20",
pages = "3742--3751",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "10",

}

TY - JOUR

T1 - Characterization of growth-differentiation factor 15, a transforming growth factor β superfamily member induced following liver injury

AU - Hsiao, Edward C.

AU - Koniaris, Leonidas G.

AU - Zimmers-Koniaris, Teresa

AU - Sebald, Suzanne M.

AU - Huynh, Thanh V.

AU - Lee, Se Jin

PY - 2000/5

Y1 - 2000/5

N2 - We have identified a new murine transforming growth factor β superfamily member, growth-differentiation factor 15 (Gdf15), that is expressed at highest levels in adult liver. As determined by Northern analysis, the expression of Gdf15 in liver was rapidly and dramatically up- regulated following various surgical and chemical treatments that cause acute liver injury and regeneration. In situ hybridization analysis revealed distinct patterns of Gdf15 mRNA localization that appeared to reflect the known patterns of hepatocyte injury in each experimental treatment. In addition, treatment of two hepatocyte-like cell lines with either carbon tetrachloride or heat shock induced Gdf15 mRNA expression, indicating that direct cellular injury can induce Gdf15 expression in the absence of other cell types, such as inflammatory cells. In order to investigate the potential functions of Gdf15, we created Gdf15 null mice by gene targeting. Homozygous null mice were viable and fertile. Despite the dramatic regulation of Gdf15 expression observed in the partial-hepatectomy and carbon tetrachloride injury models, we found no differences in the injury responses between homozygous null mutants and wild-type mice. Our findings suggest either that Gdf15 does not have a regulatory role in liver injury and regeneration or that Gdf15 function within the liver is redundant with that of other signaling molecules.

AB - We have identified a new murine transforming growth factor β superfamily member, growth-differentiation factor 15 (Gdf15), that is expressed at highest levels in adult liver. As determined by Northern analysis, the expression of Gdf15 in liver was rapidly and dramatically up- regulated following various surgical and chemical treatments that cause acute liver injury and regeneration. In situ hybridization analysis revealed distinct patterns of Gdf15 mRNA localization that appeared to reflect the known patterns of hepatocyte injury in each experimental treatment. In addition, treatment of two hepatocyte-like cell lines with either carbon tetrachloride or heat shock induced Gdf15 mRNA expression, indicating that direct cellular injury can induce Gdf15 expression in the absence of other cell types, such as inflammatory cells. In order to investigate the potential functions of Gdf15, we created Gdf15 null mice by gene targeting. Homozygous null mice were viable and fertile. Despite the dramatic regulation of Gdf15 expression observed in the partial-hepatectomy and carbon tetrachloride injury models, we found no differences in the injury responses between homozygous null mutants and wild-type mice. Our findings suggest either that Gdf15 does not have a regulatory role in liver injury and regeneration or that Gdf15 function within the liver is redundant with that of other signaling molecules.

UR - http://www.scopus.com/inward/record.url?scp=0034056778&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034056778&partnerID=8YFLogxK

U2 - 10.1128/MCB.20.10.3742-3751.2000

DO - 10.1128/MCB.20.10.3742-3751.2000

M3 - Article

VL - 20

SP - 3742

EP - 3751

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 10

ER -