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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2010.1
- 수록면
- 428 - 436 (9page)
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Inadequate apoptosis contributes to synovial hyperplasia in rheumatoid arthritis (RA). Recent study shows that low expression of Puma might be partially responsible for the decreased apoptosis of fibroblast-like synoviocytes (FLS). Slug, a highly conserved zinc finger transcriptional repressor, is known to antagonize apoptosis of hematopoietic progenitor cells by repressing Puma transactivation. In this study,we examined the expression and function of Slug in RA FLS. Slug mRNA expression was measured in the synovial tissue (ST) and FLS obtained from RA and osteoarthritis patients. Slug and Puma mRNA expression in FLS by apoptotic stimuli were measured by real-time PCR analysis. FLS were transfected with control siRNA or Slug siRNA. Apoptosis was quantified by trypan blue exclusion, DNA fragmentation and caspase-3assay. RA ST expressed higher level of Slug mRNA compared with osteoarthritis ST. Slug was significantly induced by hydrogen peroxide (H2O2) but not by exogenous p53 in RA FLS. Puma induction by H2O2stimulation was significantly higher in Slug siRNA-transfected FLS compared with control siRNA-transfected FLS. After H2O2 stimulation, viable cell number was significantly lower in Slug siRNA-transfected FLS compared with control siRNA-transfected FLS. Apoptosis enhancing effect of Slug siRNA was further confirmed by ELISA that detects cytoplasmic histone-associated DNA fragments and caspase-3 assay. These data demonstrate that Slug is overexpressed in RA ST and that suppression of Slug gene facilitates apoptosis of FLS by increasing Puma transactivation. Slug may therefore represent a potential therapeutic target in RA.
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참고문헌 (26)
참고문헌 신청
Arnett FC / 1988 / The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis / Arthritis Rheum 31 : 315 ~ 324
Catalano A / 2004 / Induction of stem cell factor/c-Kit/slug signal transduction in multidrug-resistant malignant mesothelioma cells / J Biol Chem 279 : 46706 ~ 46714
Ceponis A / 1999 / A comparative quantitative morphometric study of cell apoptosis in synovial membranes in psoriatic, reactive and rheumatoid arthritis / Rheumatology 38 : 4
Cha HS / 2006 / PUMA regulation and proapoptotic effects in fibroblast-like synoviocytes / Arthritis Rheum 54 : 587 ~ 592
Chipuk JE / 2005 / PUMA couples the nuclear and cytoplasmic proapoptotic function of p53 / Science 309 : 1732 ~ 1735
Catalano A / 2004 / Induction of stem cell factor/c-Kit/slug signal transduction in multidrug-resistant malignant mesothelioma cells / J Biol Chem 279 : 46706 ~ 46714
Ceponis A / 1999 / A comparative quantitative morphometric study of cell apoptosis in synovial membranes in psoriatic, reactive and rheumatoid arthritis / Rheumatology 38 : 4
Cha HS / 2006 / PUMA regulation and proapoptotic effects in fibroblast-like synoviocytes / Arthritis Rheum 54 : 587 ~ 592
Chipuk JE / 2005 / PUMA couples the nuclear and cytoplasmic proapoptotic function of p53 / Science 309 : 1732 ~ 1735
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