The lipopolysaccharide-triggered mesangial transcriptome: Evaluating the role of interferon regulatory factor-1

Yuyang Fu, Chun Xie, Mei Yan, Quan Li, Jae Won Joh, Christopher Lu, Chandra Mohan

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background. Presently, we do not have a clear picture of how the mesangial transcriptome evolves following stimulation. The present study was designed to address this, using an innate trigger to stimulate murine mesangial cells. Methods. Three independent mesangial cell lines derived from C57BL/6 mice were stimulated with lipopolysaccharide (LPS). The mesangial cell transcriptomes were defined 1,6,24, and 60 hours poststimulation with LPS, using a 17,000 gene oligonucleotide array. Results. Interferon regulatory factor-1 (IRF-1), ScyA2/ MCP1, ScyA20/MIP3α (ScyB1/Grol, and ScyB2/MIP2α/Gro2 were the earliest genes to be hyperexpressed after LPS stimulation. Later-appearing genes included ScyA7/MCP3, ScyD1/ fractalkine, GM-CSF/CSF-2, PDGF, epiregulin, NfKb, C/EBP, TIMP-1, MMP11, MMP13, PTGS2/COX2, SpI2-1, Spp1, PAI-1, VCAM-1, C3, and defensin-β1, among others. Several of these changes were validated by real-time polymerase chain reaction (PCR) or enzyme-linked immunosorbent assay (ELISA). Rapid IRF-1 hyperexpression was also noted following stimulation of mesangial cells with peptidoglycan, poly I:poly C, interferon-γ ?(IFN-γ), and heat-aggregated IgG. However, the blocking of IRF-1 using RNA interference and the use of mesangial cells isolated from IRF-1-deficient mice could not substantiate an obligatory role for IRF-1 in LPS-induced mesangial cell activation. Likewise, IRF-1 deficiency did not impact the development of anti-glomerular basement membrane (GBM)-induced immune nephritis. Conclusion. Innate stimuli such as LPS appear to trigger successive waves of mesangial cell gene expression. Although IRF-1 surfaces as an "early-on, early-off" transcription factor following several different triggers, it does not appear to be an essential molecule for mesangial cell activation by innate triggers or for anti-GBM disease.

Original languageEnglish (US)
Pages (from-to)1350-1361
Number of pages12
JournalKidney International
Volume67
Issue number4
DOIs
StatePublished - Apr 2005

Fingerprint

Interferon Regulatory Factor-1
Mesangial Cells
Transcriptome
Lipopolysaccharides
Granulocyte-Macrophage Colony-Stimulating Factor
Chemokine CX3CL1
Anti-Glomerular Basement Membrane Disease
Genes
Poly C
Defensins
Poly I-C
Glomerular Basement Membrane
Tissue Inhibitor of Metalloproteinase-1
Vascular Cell Adhesion Molecule-1
Peptidoglycan
Nephritis
Plasminogen Activator Inhibitor 1
Cyclooxygenase 2
RNA Interference
Oligonucleotide Array Sequence Analysis

Keywords

  • Chemokines
  • Glomerulonephritis
  • Lupus
  • Mesangial
  • Microarray

ASJC Scopus subject areas

  • Nephrology

Cite this

The lipopolysaccharide-triggered mesangial transcriptome : Evaluating the role of interferon regulatory factor-1. / Fu, Yuyang; Xie, Chun; Yan, Mei; Li, Quan; Joh, Jae Won; Lu, Christopher; Mohan, Chandra.

In: Kidney International, Vol. 67, No. 4, 04.2005, p. 1350-1361.

Research output: Contribution to journalArticle

Fu, Yuyang ; Xie, Chun ; Yan, Mei ; Li, Quan ; Joh, Jae Won ; Lu, Christopher ; Mohan, Chandra. / The lipopolysaccharide-triggered mesangial transcriptome : Evaluating the role of interferon regulatory factor-1. In: Kidney International. 2005 ; Vol. 67, No. 4. pp. 1350-1361.
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abstract = "Background. Presently, we do not have a clear picture of how the mesangial transcriptome evolves following stimulation. The present study was designed to address this, using an innate trigger to stimulate murine mesangial cells. Methods. Three independent mesangial cell lines derived from C57BL/6 mice were stimulated with lipopolysaccharide (LPS). The mesangial cell transcriptomes were defined 1,6,24, and 60 hours poststimulation with LPS, using a 17,000 gene oligonucleotide array. Results. Interferon regulatory factor-1 (IRF-1), ScyA2/ MCP1, ScyA20/MIP3α (ScyB1/Grol, and ScyB2/MIP2α/Gro2 were the earliest genes to be hyperexpressed after LPS stimulation. Later-appearing genes included ScyA7/MCP3, ScyD1/ fractalkine, GM-CSF/CSF-2, PDGF, epiregulin, NfKb, C/EBP, TIMP-1, MMP11, MMP13, PTGS2/COX2, SpI2-1, Spp1, PAI-1, VCAM-1, C3, and defensin-β1, among others. Several of these changes were validated by real-time polymerase chain reaction (PCR) or enzyme-linked immunosorbent assay (ELISA). Rapid IRF-1 hyperexpression was also noted following stimulation of mesangial cells with peptidoglycan, poly I:poly C, interferon-γ ?(IFN-γ), and heat-aggregated IgG. However, the blocking of IRF-1 using RNA interference and the use of mesangial cells isolated from IRF-1-deficient mice could not substantiate an obligatory role for IRF-1 in LPS-induced mesangial cell activation. Likewise, IRF-1 deficiency did not impact the development of anti-glomerular basement membrane (GBM)-induced immune nephritis. Conclusion. Innate stimuli such as LPS appear to trigger successive waves of mesangial cell gene expression. Although IRF-1 surfaces as an {"}early-on, early-off{"} transcription factor following several different triggers, it does not appear to be an essential molecule for mesangial cell activation by innate triggers or for anti-GBM disease.",
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AU - Joh, Jae Won

AU - Lu, Christopher

AU - Mohan, Chandra

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N2 - Background. Presently, we do not have a clear picture of how the mesangial transcriptome evolves following stimulation. The present study was designed to address this, using an innate trigger to stimulate murine mesangial cells. Methods. Three independent mesangial cell lines derived from C57BL/6 mice were stimulated with lipopolysaccharide (LPS). The mesangial cell transcriptomes were defined 1,6,24, and 60 hours poststimulation with LPS, using a 17,000 gene oligonucleotide array. Results. Interferon regulatory factor-1 (IRF-1), ScyA2/ MCP1, ScyA20/MIP3α (ScyB1/Grol, and ScyB2/MIP2α/Gro2 were the earliest genes to be hyperexpressed after LPS stimulation. Later-appearing genes included ScyA7/MCP3, ScyD1/ fractalkine, GM-CSF/CSF-2, PDGF, epiregulin, NfKb, C/EBP, TIMP-1, MMP11, MMP13, PTGS2/COX2, SpI2-1, Spp1, PAI-1, VCAM-1, C3, and defensin-β1, among others. Several of these changes were validated by real-time polymerase chain reaction (PCR) or enzyme-linked immunosorbent assay (ELISA). Rapid IRF-1 hyperexpression was also noted following stimulation of mesangial cells with peptidoglycan, poly I:poly C, interferon-γ ?(IFN-γ), and heat-aggregated IgG. However, the blocking of IRF-1 using RNA interference and the use of mesangial cells isolated from IRF-1-deficient mice could not substantiate an obligatory role for IRF-1 in LPS-induced mesangial cell activation. Likewise, IRF-1 deficiency did not impact the development of anti-glomerular basement membrane (GBM)-induced immune nephritis. Conclusion. Innate stimuli such as LPS appear to trigger successive waves of mesangial cell gene expression. Although IRF-1 surfaces as an "early-on, early-off" transcription factor following several different triggers, it does not appear to be an essential molecule for mesangial cell activation by innate triggers or for anti-GBM disease.

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