Targeting Intra-Pulmonary P53-Dependent Long Non-Coding RNA Expression as a Therapeutic Intervention for Systemic Lupus Erythematosus-Associated Diffuse Alveolar Hemorrhage
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作者:
Chen, Yi-Cheng
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Natl Cheng Kung Univ, Dept Internal Med, Med Coll & Hosp, Tainan 70403, Taiwan
Ditmanson Med Fdn, Chiayi Christian Hosp, Dept Med Res, Chiayi 600566, Taiwan
Natl Cheng Kung Univ, Dept Biochem & Mol Biol, Med Coll, Tainan 70403, TaiwanNatl Cheng Kung Univ, Dept Internal Med, Med Coll & Hosp, Tainan 70403, Taiwan
Chen, Yi-Cheng
[1
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Chou, Yu-Chi
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Acad Sinica, Biomed Translat Res Ctr, Taipei 11529, TaiwanNatl Cheng Kung Univ, Dept Internal Med, Med Coll & Hosp, Tainan 70403, Taiwan
Chou, Yu-Chi
[4
]
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Hsieh, Yu-Tung
[5
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Kuo, Pin-Yu
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Natl Cheng Kung Univ, Dept Microbiol & Immunol, Med Coll, Tainan 70403, TaiwanNatl Cheng Kung Univ, Dept Internal Med, Med Coll & Hosp, Tainan 70403, Taiwan
Kuo, Pin-Yu
[5
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Yang, Mei-Lin
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Natl Cheng Kung Univ, Dept Microbiol & Immunol, Med Coll, Tainan 70403, TaiwanNatl Cheng Kung Univ, Dept Internal Med, Med Coll & Hosp, Tainan 70403, Taiwan
Yang, Mei-Lin
[5
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Chong, Hao-Earn
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Natl Cheng Kung Univ, Dept Internal Med, Med Coll & Hosp, Tainan 70403, TaiwanNatl Cheng Kung Univ, Dept Internal Med, Med Coll & Hosp, Tainan 70403, Taiwan
Chong, Hao-Earn
[1
]
Wu, Chao-Liang
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Natl Cheng Kung Univ, Dept Biochem & Mol Biol, Med Coll, Tainan 70403, TaiwanNatl Cheng Kung Univ, Dept Internal Med, Med Coll & Hosp, Tainan 70403, Taiwan
Wu, Chao-Liang
[3
]
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Shiau, Ai-Li
[5
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Wang, Chrong-Reen
[1
,5
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机构:
[1] Natl Cheng Kung Univ, Dept Internal Med, Med Coll & Hosp, Tainan 70403, Taiwan
[2] Ditmanson Med Fdn, Chiayi Christian Hosp, Dept Med Res, Chiayi 600566, Taiwan
[3] Natl Cheng Kung Univ, Dept Biochem & Mol Biol, Med Coll, Tainan 70403, Taiwan
[4] Acad Sinica, Biomed Translat Res Ctr, Taipei 11529, Taiwan
[5] Natl Cheng Kung Univ, Dept Microbiol & Immunol, Med Coll, Tainan 70403, Taiwan
Diffuse alveolar hemorrhage (DAH) in systemic lupus erythematosus (SLE) is associated with significant mortality, requiring a thorough understanding of its complex mechanisms to develop novel therapeutics for disease control. Activated p53-dependent apoptosis with dysregulated long non-coding RNA (lncRNA) expression is involved in the SLE pathogenesis and correlated with clinical activity. We examined the expression of apoptosis-related p53-dependent lncRNA, including H19, HOTAIR and lincRNA-p21 in SLE-associated DAH patients. Increased lincRNA-p21 levels were detected in circulating mononuclear cells, mainly in CD4+ and CD14+ cells. Higher expression of p53, lincRNA-p21 and cell apoptosis was identified in lung tissues. Lentivirus-based short hairpin RNA (shRNA)-transduced stable transfectants were created for examining the targeting efficacy in lncRNA. Under pristane stimulation, alveolar epithelial cells had increased p53, lincRNA-p21 and downstream Bax levels with elevated apoptotic ratios. After pristane injection, C57/BL6 mice developed DAH with increased pulmonary expression of p53, lincRNA-p21 and cell apoptosis. Intra-pulmonary delivery of shRNA targeting lincRNA-p21 reduced hemorrhage frequencies and improved anemia status through decreasing Bax expression and cell apoptosis. Our findings demonstrate increased p53-dependent lncRNA expression with accelerated cell apoptosis in the lungs of SLE-associated DAH patients, and show the therapeutic potential of targeting intra-pulmonary lncRNA expression in a pristane-induced model of DAH.
机构:
Menoufia Univ, Fac Med, Clin Pathol Dept, Shibin Al Kawm 32511, EgyptMenoufia Univ, Fac Med, Clin Pathol Dept, Shibin Al Kawm 32511, Egypt
Tawfeek, Gehan Abd-Elfatah
Kasem, Heba
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Menoufia Univ, Fac Med, Internal Med Dept, Nephrol Unit, Shibin Al Kawm 32511, EgyptMenoufia Univ, Fac Med, Clin Pathol Dept, Shibin Al Kawm 32511, Egypt
Kasem, Heba
Abdallah, Eman Ali
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Menoufia Univ, Fac Med, Rheumatol Rehabil & Phys Med Dept, Shibin Al Kawm 32511, Egypt
King Faisal Univ, Coll Med, Internal Med Dept, Al Hasa 31982, Saudi ArabiaMenoufia Univ, Fac Med, Clin Pathol Dept, Shibin Al Kawm 32511, Egypt
Abdallah, Eman Ali
Almulhim, Mohammed
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King Faisal Univ, Coll Med, Internal Med Dept, Al Hasa 31982, Saudi ArabiaMenoufia Univ, Fac Med, Clin Pathol Dept, Shibin Al Kawm 32511, Egypt
Almulhim, Mohammed
Almulhim, Abdullah
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King Faisal Univ, Coll Med, Family & Community Med Dept, Al Hasa 31982, Saudi ArabiaMenoufia Univ, Fac Med, Clin Pathol Dept, Shibin Al Kawm 32511, Egypt
Almulhim, Abdullah
Albarqi, Mohammed
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King Faisal Univ, Coll Med, Family & Community Med Dept, Al Hasa 31982, Saudi ArabiaMenoufia Univ, Fac Med, Clin Pathol Dept, Shibin Al Kawm 32511, Egypt
Albarqi, Mohammed
Elzorkany, Khaled Mohamed Amin
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Menoufia Univ, Fac Med, Internal Med Dept, Nephrol Unit, Shibin Al Kawm 32511, Egypt
King Faisal Univ, Coll Med, Internal Med Dept, Al Hasa 31982, Saudi ArabiaMenoufia Univ, Fac Med, Clin Pathol Dept, Shibin Al Kawm 32511, Egypt
机构:
Masaryk Univ, Cent European Inst Technol, Brno 62500, Czech RepublicMasaryk Univ, Cent European Inst Technol, Brno 62500, Czech Republic
Thorenoor, Nithyananda
Faltejskova-Vychytilova, Petra
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Masaryk Univ, Cent European Inst Technol, Brno 62500, Czech Republic
Masaryk Mem Canc Inst, Dept Comprehens Canc Care, Brno 65653, Czech RepublicMasaryk Univ, Cent European Inst Technol, Brno 62500, Czech Republic
Faltejskova-Vychytilova, Petra
Hombach, Sonja
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Univ Regensburg, Inst Biochem Genet & Microbiol, D-93053 Regensburg, GermanyMasaryk Univ, Cent European Inst Technol, Brno 62500, Czech Republic
Hombach, Sonja
Mlcochova, Jitka
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Masaryk Univ, Cent European Inst Technol, Brno 62500, Czech RepublicMasaryk Univ, Cent European Inst Technol, Brno 62500, Czech Republic
Mlcochova, Jitka
Kretz, Markus
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Univ Regensburg, Inst Biochem Genet & Microbiol, D-93053 Regensburg, GermanyMasaryk Univ, Cent European Inst Technol, Brno 62500, Czech Republic
Kretz, Markus
Svoboda, Marek
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Masaryk Mem Canc Inst, Dept Comprehens Canc Care, Brno 65653, Czech RepublicMasaryk Univ, Cent European Inst Technol, Brno 62500, Czech Republic
Svoboda, Marek
Slaby, Ondrej
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Masaryk Univ, Cent European Inst Technol, Brno 62500, Czech Republic
Masaryk Mem Canc Inst, Dept Comprehens Canc Care, Brno 65653, Czech RepublicMasaryk Univ, Cent European Inst Technol, Brno 62500, Czech Republic
机构:
Sapporo Med Univ, Med Genome Sci, Inst Frontier Med, Sapporo, Hokkaido, JapanSapporo Med Univ, Med Genome Sci, Inst Frontier Med, Sapporo, Hokkaido, Japan
Idogawa, Masashi
Koizumi, Masayo
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Sapporo Med Univ, Med Genome Sci, Inst Frontier Med, Sapporo, Hokkaido, JapanSapporo Med Univ, Med Genome Sci, Inst Frontier Med, Sapporo, Hokkaido, Japan
Koizumi, Masayo
Tange, Shoichiro
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Sapporo Med Univ, Med Genome Sci, Inst Frontier Med, Sapporo, Hokkaido, JapanSapporo Med Univ, Med Genome Sci, Inst Frontier Med, Sapporo, Hokkaido, Japan
Tange, Shoichiro
Hirano, Tomomi
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Sapporo Med Univ, Med Genome Sci, Inst Frontier Med, Sapporo, Hokkaido, JapanSapporo Med Univ, Med Genome Sci, Inst Frontier Med, Sapporo, Hokkaido, Japan
Hirano, Tomomi
Okubo, Yosuke
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Sapporo Med Univ, Med Genome Sci, Inst Frontier Med, Sapporo, Hokkaido, JapanSapporo Med Univ, Med Genome Sci, Inst Frontier Med, Sapporo, Hokkaido, Japan
Okubo, Yosuke
Tokino, Takashi
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Sapporo Med Univ, Med Genome Sci, Inst Frontier Med, Sapporo, Hokkaido, JapanSapporo Med Univ, Med Genome Sci, Inst Frontier Med, Sapporo, Hokkaido, Japan