Lysosome-related genes are regulated in the orbital fat of patients with Graves' ophthalmopathy

Mei Hsiu Chen, Shu Lang Liao, Ming Hong Chen, Pei Ling Tsou, Mei Ju Shih, Tien Chun Chang, Lee Ming Chuang

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

PURPOSE. The molecular mechanism involved in the hypertrophy of the orbital fat in patients with Graves' ophthalmopathy or thyroid eye disease (TED) remains unclear. Comparison of genome-wide expression profiles may help in the search for the gene sets involved in TED. METHODS. Twenty-five orbital adipose tissue specimens were obtained, from which the RNA was isolated. Four of the tissue specimens (from four individuals, two with TED and two control subjects) were subjected to cDNA microarray analysis. The data were analyzed by the gene set enrichment analysis (GSEA) to survey the biological pathways involved in the pathogenesis of TED. Messenger RNA levels of some topranked genes in GSEA-selected pathways are validated by quantitative PCR (QPCR). RESULTS. The expression of specific gene sets related to lytic vacuoles, lysosomes, and vacuoles were different between the specimens obtained from patients with TED and control subjects (P < 0.001). These three gene sets overlapped. For QPCR, four top-ranked genes were selected from these overlapping gene sets and another one that related to visual failure, using 21 independent samples of patients with TED (n = 15) and control subjects (n = 6). The results showed that ceroid-lipofuscinosis, neuronal 2, late infantile (CLN2; P = 0.044) and ceroid-lipofuscinosis, neuronal 3, juvenile (CLN3, which related to visual failure; P = 0.012) were significantly downregulated in the orbital fat of patients with TED. The expression of the β subunit of hexosaminidase A (HEXB) was reduced as well, but the change did not reach statistical significance (P = 0.058). CONCLUSIONS. Lysosome-related genes, such as CLN2, CLN3, and HEXB, may be involved in the pathogenesis of adipose tissue hypertrophy in TED.

Original languageEnglish
Pages (from-to)4760-4764
Number of pages5
JournalInvestigative Ophthalmology and Visual Science
Volume49
Issue number11
DOIs
Publication statusPublished - Nov 1 2008
Externally publishedYes

Fingerprint

Graves Ophthalmopathy
Eye Diseases
Thyroid Diseases
Lysosomes
Fats
Genes
Vacuoles
Hypertrophy
Adipose Tissue
Hexosaminidase A
Overlapping Genes
Neuronal Ceroid-Lipofuscinoses
Polymerase Chain Reaction
Microarray Analysis
Oligonucleotide Array Sequence Analysis
Down-Regulation
Genome
RNA
Gene Expression
Messenger RNA

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Lysosome-related genes are regulated in the orbital fat of patients with Graves' ophthalmopathy. / Chen, Mei Hsiu; Liao, Shu Lang; Chen, Ming Hong; Tsou, Pei Ling; Shih, Mei Ju; Chang, Tien Chun; Chuang, Lee Ming.

In: Investigative Ophthalmology and Visual Science, Vol. 49, No. 11, 01.11.2008, p. 4760-4764.

Research output: Contribution to journalArticle

Chen, Mei Hsiu ; Liao, Shu Lang ; Chen, Ming Hong ; Tsou, Pei Ling ; Shih, Mei Ju ; Chang, Tien Chun ; Chuang, Lee Ming. / Lysosome-related genes are regulated in the orbital fat of patients with Graves' ophthalmopathy. In: Investigative Ophthalmology and Visual Science. 2008 ; Vol. 49, No. 11. pp. 4760-4764.
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abstract = "PURPOSE. The molecular mechanism involved in the hypertrophy of the orbital fat in patients with Graves' ophthalmopathy or thyroid eye disease (TED) remains unclear. Comparison of genome-wide expression profiles may help in the search for the gene sets involved in TED. METHODS. Twenty-five orbital adipose tissue specimens were obtained, from which the RNA was isolated. Four of the tissue specimens (from four individuals, two with TED and two control subjects) were subjected to cDNA microarray analysis. The data were analyzed by the gene set enrichment analysis (GSEA) to survey the biological pathways involved in the pathogenesis of TED. Messenger RNA levels of some topranked genes in GSEA-selected pathways are validated by quantitative PCR (QPCR). RESULTS. The expression of specific gene sets related to lytic vacuoles, lysosomes, and vacuoles were different between the specimens obtained from patients with TED and control subjects (P < 0.001). These three gene sets overlapped. For QPCR, four top-ranked genes were selected from these overlapping gene sets and another one that related to visual failure, using 21 independent samples of patients with TED (n = 15) and control subjects (n = 6). The results showed that ceroid-lipofuscinosis, neuronal 2, late infantile (CLN2; P = 0.044) and ceroid-lipofuscinosis, neuronal 3, juvenile (CLN3, which related to visual failure; P = 0.012) were significantly downregulated in the orbital fat of patients with TED. The expression of the β subunit of hexosaminidase A (HEXB) was reduced as well, but the change did not reach statistical significance (P = 0.058). CONCLUSIONS. Lysosome-related genes, such as CLN2, CLN3, and HEXB, may be involved in the pathogenesis of adipose tissue hypertrophy in TED.",
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T1 - Lysosome-related genes are regulated in the orbital fat of patients with Graves' ophthalmopathy

AU - Chen, Mei Hsiu

AU - Liao, Shu Lang

AU - Chen, Ming Hong

AU - Tsou, Pei Ling

AU - Shih, Mei Ju

AU - Chang, Tien Chun

AU - Chuang, Lee Ming

PY - 2008/11/1

Y1 - 2008/11/1

N2 - PURPOSE. The molecular mechanism involved in the hypertrophy of the orbital fat in patients with Graves' ophthalmopathy or thyroid eye disease (TED) remains unclear. Comparison of genome-wide expression profiles may help in the search for the gene sets involved in TED. METHODS. Twenty-five orbital adipose tissue specimens were obtained, from which the RNA was isolated. Four of the tissue specimens (from four individuals, two with TED and two control subjects) were subjected to cDNA microarray analysis. The data were analyzed by the gene set enrichment analysis (GSEA) to survey the biological pathways involved in the pathogenesis of TED. Messenger RNA levels of some topranked genes in GSEA-selected pathways are validated by quantitative PCR (QPCR). RESULTS. The expression of specific gene sets related to lytic vacuoles, lysosomes, and vacuoles were different between the specimens obtained from patients with TED and control subjects (P < 0.001). These three gene sets overlapped. For QPCR, four top-ranked genes were selected from these overlapping gene sets and another one that related to visual failure, using 21 independent samples of patients with TED (n = 15) and control subjects (n = 6). The results showed that ceroid-lipofuscinosis, neuronal 2, late infantile (CLN2; P = 0.044) and ceroid-lipofuscinosis, neuronal 3, juvenile (CLN3, which related to visual failure; P = 0.012) were significantly downregulated in the orbital fat of patients with TED. The expression of the β subunit of hexosaminidase A (HEXB) was reduced as well, but the change did not reach statistical significance (P = 0.058). CONCLUSIONS. Lysosome-related genes, such as CLN2, CLN3, and HEXB, may be involved in the pathogenesis of adipose tissue hypertrophy in TED.

AB - PURPOSE. The molecular mechanism involved in the hypertrophy of the orbital fat in patients with Graves' ophthalmopathy or thyroid eye disease (TED) remains unclear. Comparison of genome-wide expression profiles may help in the search for the gene sets involved in TED. METHODS. Twenty-five orbital adipose tissue specimens were obtained, from which the RNA was isolated. Four of the tissue specimens (from four individuals, two with TED and two control subjects) were subjected to cDNA microarray analysis. The data were analyzed by the gene set enrichment analysis (GSEA) to survey the biological pathways involved in the pathogenesis of TED. Messenger RNA levels of some topranked genes in GSEA-selected pathways are validated by quantitative PCR (QPCR). RESULTS. The expression of specific gene sets related to lytic vacuoles, lysosomes, and vacuoles were different between the specimens obtained from patients with TED and control subjects (P < 0.001). These three gene sets overlapped. For QPCR, four top-ranked genes were selected from these overlapping gene sets and another one that related to visual failure, using 21 independent samples of patients with TED (n = 15) and control subjects (n = 6). The results showed that ceroid-lipofuscinosis, neuronal 2, late infantile (CLN2; P = 0.044) and ceroid-lipofuscinosis, neuronal 3, juvenile (CLN3, which related to visual failure; P = 0.012) were significantly downregulated in the orbital fat of patients with TED. The expression of the β subunit of hexosaminidase A (HEXB) was reduced as well, but the change did not reach statistical significance (P = 0.058). CONCLUSIONS. Lysosome-related genes, such as CLN2, CLN3, and HEXB, may be involved in the pathogenesis of adipose tissue hypertrophy in TED.

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