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mTORC2-dependent regulationof Gilz expression

Başlık çevirisi mevcut değil.

  1. Tez No: 706882
  2. Yazar: HATİCE BURCU ŞİŞLİ
  3. Danışmanlar: PROF. KWON HYOCKMAN
  4. Tez Türü: Yüksek Lisans
  5. Konular: Biyoteknoloji, Biotechnology
  6. Anahtar Kelimeler: Belirtilmemiş.
  7. Yıl: 2018
  8. Dil: İngilizce
  9. Üniversite: Hankuk University of Foreign Studies
  10. Enstitü: Yurtdışı Enstitü
  11. Ana Bilim Dalı: Belirtilmemiş.
  12. Bilim Dalı: Belirtilmemiş.
  13. Sayfa Sayısı: 37

Özet

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Özet (Çeviri)

Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disorder affecting nearly 1% of the population and characterized by progressive joint destruction and bone erosion. Glucocorticoids (GCs), as the major medication to suppress the inflammation, are highly effective but come with severe side effects including but not limited to bone loss, diabetes mellitus, hypertension and infection. In search of alternative therapeutic strategies to avoid these detrimental side effects, GILZ, as the antiinflammatory effect mediator of GCs, and the mediator of bone anabolic actions, emerged as a potential target. These key functions of GILZ directed researchers to find a non-steroid drug inducing GILZ expression. In this study, a novel non-steroid compound called Mini2001 (Mini) was used to induce expression of GILZ independently from GC-induced pathway. Next-generation sequencing (NGS) results of adipose-derived stem cells (ADSCs) treated with glycosylated form of this compound, Hub3115 (Hub), showed increased expression of GILZ. Here, I tried to shed light to the mechanism behind Hub-induced GILZ expression. According to the data, GILZ expression is not only induced by Mini, but also induced synergistically by GC and Mini. Although Mini induces FoxO3 nuclear localization and its binding to FHRE, the interaction between FoxO3a and FHRE at GILZ promoter is not the primary reason for enhanced GILZ expression. Mini increases c-Myc phosphorylation at Ser62, but c-Myc protein level decreases progressively in a long-term Mini treatment. Phosphorylation of Ser62 of c-Myc activates c-Myc, and the GILZ promoter contains 2 three c-Myc binding sites. By considering the results, activation of c-Myc by phosphorylation and its-binding to c-Myc binding element on GILZ promoter may be the main reason for the enhanced GILZ expression and this effect of Mini is likely to be mediated by mTORC2 inhibition.

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