안와섬유모세포의 지방세포 분화에 대한 혼합 갱글리오사이드의 영향
Effect of Gangliosides Mixture on Differentiation of Orbital Fibroblasts into Adipocytes
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목적: 갑상샘눈병증의 병리기전 중 안와섬유모세포의 지방세포로의 분화에 대한 갱글리오사이드의 역할의 가능성을 밝히고자 하였다. 대상과 방법: 갑상샘눈병증이 없으며 비염증성 안와 질환을 이유로 시행된 안와 수술 시 얻은 안와 지방 조직으로부터 정상 안와섬유모 세포를 일차배양하여, 갱글리오사이드의 여러 아형이 혼합되어 있는 상용화된 혼합 갱글리오사이드를 처리한 후 세포의 형태 변화를 관찰하였다. 지방세포 분화 여부를 밝히기 위하여 oil red-O 염색 및 지방세포 분화와 관련된 유전자에 대한 RT-PCR을 시행하였다. 결과: 안와섬유모세포에 혼합 갱글리오사이드를 처리한 결과, 농도에 비례하여 세포의 형태 변화가 관찰되었으며, 피부섬유모세포와 지방전세포는 이러한 형태 변화가 관찰되지 않았다. 혼합 갱글리오사이드 처리 결과, 일부 안와섬유모세포의 지방세포로의 분화가 관찰되었으며, 지방세포 분화 연관 유전자의 mRNA의 증가가 관찰되었다. 결론: 본 연구 결과들로부터, 갱글리오사이드가 안와섬유모세포의 지방세포로의 분화와 관련한 갑상샘눈병증의 병리 기전에 관여할 가능성을 제시한다.
Abstract
Purpose: To investigate the role of gangliosides in the differentiation of orbital fibroblasts into adipocytes, a component in the pathogenesis of Graves’ ophthalmopathy. Methods: Orbital tissues were obtained during orbital surgery for subjects without Graves’ ophthalmopathy or other inflammatory orbital disease, and orbital fibroblasts were primarily cultured from each obtained tissue. Morphological examination of orbital fibroblasts was performed after treatment with commercially available gangliosides mixture (Gmix) comprised of several subtypes. To determine the effect of Gmix on the differentiation of orbital fibroblasts into adipocytes and the differentiation-related genes, Oil Red-O staining and RT-PCR were performed. Results: The treatment with Gmix induced the morphological changes, which at least in part were explained with the differentiation of orbital fibroblasts into adipocytes in accordance with the increase of mRNA level of genes known to be related to adipogenesis, whereas dermal fibroblasts and preadipocytes were irresponsive to the same treatment. Conclusions: The results from the present study suggest gangliosides may have a role in pathologic mechanisms of Graves’ ophthalmopathy by the induction of differentiation of orbital fibroblasts into adipocytes.
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