Ganglioside GT1b increases hyaluronic acid synthase 2 via PI3K activation with TLR2 dependence in orbital fibroblasts from thyroid eye disease patients
- 주제(키워드) Orbital fibroblast , Phosphoinositide 3-kinase , Thyroid eye disease , Toll-like receptor 2 , Trisialoganglioside 1b
- 주제(기타) Biochemistry & Molecular Biology
- 설명문(일반) [Yoo, Hyun Kyu; Hwang, Hye Suk; Kook, Koung Hoon] Ajou Univ, Dept Ophthalmol, Sch Med, Suwon 16499, South Korea; [Park, Hyunju; Kim, Hee Ja; Choi, Youn-Hee] Ewha Womans Univ, Inflammat Canc Microenvironm Res Ctr, Dept Physiol, Sch Med, Seoul 07804, South Korea
- 등재 SCIE, SCOPUS, KCI등재
- 발행기관 KOREAN SOCIETY BIOCHEMISTRY & MOLECULAR BIOLOGY
- 발행년도 2021
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000181481
- 본문언어 영어
- Published As http://dx.doi.org/10.5483/BMBRep.2021.54.2.178
초록/요약
Thyroid eye disease (TED) is a complex autoimmune disease with a spectrum of signs. we previously reported that trisialoganglioside (GT)1b is significantly overexpressed in the orbital tissue of TED patients, and that exogenous GT1b strongly induced HA synthesis in orbital fibroblasts. However, the signaling pathway in GT1b-induced hyaluronic acid synthase (HAS) expression in orbital fibroblasts from TED patients have rarely been investigated. Here, we demonstrated that GT1b induced phosphorylation of Akt/mTOR in a dose-dependent manner in orbital fibroblasts from TED patients. Both co-treatment with a specific inhibitor for PI3K and siRNA knockdown of TLR2 attenuated GT1b-induced Akt phosphorylation. GT1b significantly induced HAS2 expression at both the transcriptional and translational level, which was suppressed by specific inhibitors of PI3K or Akt/mTOR, and by siRNA knockdown of TLR2. In conclusion, GT1b induced HAS2 in orbital fibroblasts from TED patients via activation of the PI3K-related signaling pathway, dependent on TLR2.
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