https://scholars.lib.ntu.edu.tw/handle/123456789/495669
標題: | Lysosome-related genes are regulated in the orbital fat of patients with Graves' ophthalmopathy | 作者: | Chen M.-H. SHU-LANG LIAO Chen M.-H. Tsou P.-L. Shih M.-J. TIEN-CHUN CHANG LEE-MING CHUANG |
公開日期: | 2008 | 卷: | 49 | 期: | 11 | 起(迄)頁: | 4760-4764 | 來源出版物: | Investigative Ophthalmology and Visual Science | 摘要: | 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. Copyright ? Association for Research in Vision and Ophthalmology. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-56149108241&doi=10.1167%2fiovs.08-2020&partnerID=40&md5=f75cb348bcf256ffb783cc0be6206c42 https://scholars.lib.ntu.edu.tw/handle/123456789/495669 |
ISSN: | 0146-0404 | DOI: | 10.1167/iovs.08-2020 | SDG/關鍵字: | beta actin; beta n acetylhexosaminidase A; ceroid lipofuscinosis neuronal 2 late infantile; ceroid lipofuscinosis neuronal 3 juvenile; complementary DNA; lysosome associated membrane protein; lysosome associated membrane protein 3; messenger RNA; mucolipin; protein; unclassified drug; beta n acetylhexosaminidase beta chain; biological marker; chaperone; CLN3 protein, human; HEXB protein, human; membrane protein; messenger RNA; proteinase; tripeptidyl peptidase i; tripeptidyl-peptidase I; adipose tissue; adult; article; cell vacuole; clinical article; controlled study; DNA microarray; down regulation; endocrine ophthalmopathy; female; gene expression profiling; genome analysis; human; human tissue; lipofuscinosis; lipohypertrophy; lysosome; male; microarray analysis; orbit; pathogenesis; polymerase chain reaction; priority journal; quantitative analysis; RNA isolation; signal transduction; visual impairment; biosynthesis; comparative study; endocrine ophthalmopathy; gene expression regulation; genetics; metabolism; middle aged; neuronal ceroid lipofuscinosis; orbit; pathology; Adipose Tissue; Adult; beta-Hexosaminidase beta Chain; Biological Markers; Endopeptidases; Female; Gene Expression Regulation; Graves Ophthalmopathy; Humans; Male; Membrane Glycoproteins; Microarray Analysis; Middle Aged; Molecular Chaperones; Neuronal Ceroid-Lipofuscinoses; Orbit; Polymerase Chain Reaction; RNA, Messenger |
顯示於: | 醫學系 |
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