| 대한안과학회 학술대회 발표 연제 초록 |
| 성형 F-022 |
| 일차 배양한 갑상선안병증 섬유모세포에서 치료표적으로서의 Protein tyrosine phosphatase 1B 의 병리적 역할에 대한 연구 |
1 연세대학교 의과대학 안과학교실, 시기능센터 2 연세대학교 의과대학 내과학교실, 내분비 연구센터 |
| 변형주 1, 김지영 1, 고재상 1, 이은직 2, 윤진숙 1 |
목적 : Graves’ orbitopathy(GO) is characterized as adipogenesis and inflammation of orbital fibroblast. Protein tyrosine phosphatase 1B(PTP1B) has been spotlighted as a therapeutic target of diabetes and obesity and recently, as a regulator of inflammatory signals. We investigated the role of PTP1B in primary cultures of orbital fibroblasts from GO patients and evaluated as therapeutic target. 방법 : Orbital fibroblasts were acquired from patients with GO and healthy controls. To determine the role of PTP1B, cells were transfected with siRNA of PTPN1 and maintained for 24 hours. After that, the fibroblasts were exposed to stimulations such as IL-1β, cigarette smoke extract (CSE), H2O2, and TGF-β. Release of inflammatory cytokines and production of fibrosis-related proteins were analyzed using western blot analysis and/or enzyme-linked immunosorbent assay (ELISA). The release of reactive oxygen species (ROS) was detected using an oxidant-sensitive fluorescent probe. 결과 : IL-1β , TNF-β, bovine TSH (bTSH), M22 and IGF-1 significantly increased PTP1B protein production. When PTP1B was knocked down using siRNA, IL-1β induced inflammatory cytokines were reduced significantly. PTP1B inhibition suppressed CSE- and H2O2-induced ROS synthesis. TGF-β-induced collagen Ia, a-SMA and fibronectin protein expression was significantly suppressed by PTP1B knock down. Silencing PTP1B also lowered phosphorylation of Akt, p38, and JNK signal proteins. 결론 : PTP1B inhibition shows anti-inflammatory effect as well as reducing ROS synthesis and fibrosis in GO fibroblast. It is possibly affected by Akt pathway and MAPK such as p38, JNK pathway. Modulation of PTP1B may have a therapeutic potential of the treatment of GO. |