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MITF (microphthalmia-associated transcription factor)가 멜라닌세포의 가지돌기 형성에 미치는 영향
조인숙(In Sook Jo),손경철(Kyung-Cheol Sohn),김창덕(Chang Deok Kim),이영호(Young Ho Lee) 대한체질인류학회 2016 해부·생물인류학 (Anat Biol Anthropol) Vol.29 No.1
Microphthalmia-associated transcriptian factor (MITF)는 basic-loop-helix leucine zipper family 중의 하나인 중요한 조절인자로서 멜라닌세포에서 멜라닌 형성에 관여한다. MITF는 MITF-M, MITF-A, MITF-B, MITF-C, MITF-H 및 MITF-J 등이 아형이 존재한다. MITF-M은 피부의 멜라닌세포에서 발현되며 멜라닌을 만들어내는 데 관여한다. 이전의 연구에서 MITF-A, MITF-C, MITF-H 및 MITF-J가 표피에서 발현됨을 확인하였다. 본 연구에서는 멜라닌세포에서 발현되는 MITF 아형을 확인하고 이들의 멜라닌 형성 이 외의 역할을 확인하고자 하였다. MITF-M과 MITF-A가 일차멜라닌세포 및 SK-MEL-24 흑색종 암세포에서 발현됨을 확인하였다. SK-MEL-24 흑색종 암세포에 과발현시킨 결과 세포의 멜라노솜의 이동통로가 되는 가지돌기의 길이가 MITF-M 과발현 시 주로 증가하였으며, MITF-A 과발현 시는 주로 가지돌기의 수가 유의하게 증가하였다. 가지돌기의 액틴 중합반응에 관여하는 물질 중에 하나인 Rac1이 MITF 과발현세포에서 증가하였다. 결론적으로 멜라닌세포에서 MITF-M과 MITF-A는 Rac1 신호를 경유하여 가지돌기 형성을 증가시킴을 확인하였다. The microphthalmia-associated transcription factor (MITF), has been described as the master regulator of the basic helix-loop-helix leucine zipper family, involves melanogenesis in melanocytes. MITF consists of at least six isoforms, called MITF-M, MITF-A, MITF-B, MITF-C, MITF-H, and MITF-J. Previously, we found that not only MITF-M is expressed in the human hair follicle, but also MITF-A, MITF-C, MITF-H, and MITF-J isoforms are expressed in the skin. The aim of this study was to conform the MITF isoforms expressed in human skin, and investigate novel role of MITF isoforms in the melanocytes. Expression of MITF-M and MITF-A was found in primary melanoctyes and the melanoma cell lines. Interestingly, when MITF-M and MITF-A were overexpressed in the SK-MEL-24 melanoma cells by adenoviral transfection, length of the dendrites, serves as the principal conduit for melanosomes transfer, was significantly increased in the MITF-M overexpressed cells compared with the control group, and number of the dendtrites was significantly increased in the MITF-A overexpressed cells. A signal molecule involve in actin polymerization during dendrite formation, Rac1, was increased in the SK-MEL-24 melanoma cells treated with adenoviral MITF-M and MITF-A vectors. These results suggest that MITF-M and MITF-A induce dendrite formation via Rac1 signaling in the melanocytes.
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최대경 ( Dae Kyoung Choi ),이경문 ( Kyung Moon Lee ),김대훈 ( Dae Hun Kim ),이영 ( Young Lee ),손경철 ( Kyung Cheol Sohn ),김창덕 ( Chang Deok Kim ),서영준 ( Young Joon Seo ),이증훈 ( Jeung Hoon Lee ) 대한피부과학회 2010 대한피부과학회지 Vol.48 No.5
Background: Calcium plays a role in the proliferation and differentiation of keratinocytes. In a normal situation, the calcium concentration forms a gradient across the epidermal layers. Calcium is sparse in the basal layer and spinous layer. Skin organ culture is a useful model for conducting research on various aspects of skin biology. Skin organ culture systems are used for defining factors that affect homeostasis when elucidating the modulatory effects of biologic response modifiers, drugs and physical agents on the skin and also when studying complex aspects of cutaneous biology in normal and diseased skin. Objective: In this study, we investigated the effects of extracellular calcium on the epidermis in a skin organ culture. Methods: We compared the skin organ culture patterns under various culture conditions (calcium 0.1, 0.7, 1.4 and 2.0 mM). Results: H&E staining showed different phenotypes according to the calcium concentration and IHC also showed different phenotyes compared to that of keratin 10, involucrin, filaggrin, loricrin and PCNA. Conclusion: As a result, we concluded that the calcium gradient is also an important factor in skin organ culture to maintain the vivo-like environment and the appropriate calcium concentration is 1.4 mM. (Korean J Dermatol 2010;48(5):373~379)
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Immunohistochemical Study of O-GlcNAcylation in Human Skin Tumors
Young Lee(이영),Dong Kyun Hong(홍동균),Dae Kyoung Choi(최대경),Seul Ki Lim(임슬기),Kyung Cheol Sohn(손경철),Myung Im(임명),Young Joon Seo(서영준),Young Ho Lee(이영호),Jeung Hoon Lee(이증훈),Chang Deok Kim(김창덕) 대한체질인류학회 2014 해부·생물인류학 (Anat Biol Anthropol) Vol.27 No.2
단백질 전사 후 변형 (posttranslational modification)은 단백질 기능을 조절하는 기전의 하나로, 당화(gycosylation), 아세틸화 (acetylation), 메틸화 (methylation) 등을 포함한다. O-linked β-N-acetylglucosamine (OGlcNAc)에 의한 단백질 전사 후 변형은 많은 세포 반응에 관여하는 조절 기전으로 최근 연구가 많이 진행되고 있다. 특히, O-GlcNAc에 의한 단백질 전사 후 변형(O-GlcNAcylation)은 유방암, 폐암 및 대장암 등과 같은 암질환의 발병에 관여함이 보고되었다. 그러나 이러한 O-GlcNAcylation이 피부종양에 어떠한 영향을 미치는지 잘 밝혀져 있지 않다. 본 연구에서는 다양한 피부종양을 대상으로 하여 O-GlcNAcylation이 어떻게 일어나는지 면역조직화학을 통해 살펴보았다. 그 결과, 양성종양에 비해 암전구증 및 악성종양에서 전체적으로 O-GlcNAcylation이 증가해 있었다. 또한 O-GlcNAcylation을 담당하는 효소인 O-GlcNAc transferase (OGT) 및 O-GlcNAc을 제거하는 효소인 O-GlcNAcase (OGA) 발현 또한 양성종양에 비해 암전구증 및 악성종양에서 증가해 있었다. 이러한 연구 결과는 O-GlcNAcylation이 여러 피부종양의 발병에 관여함을 시사한다. O-linked β-N-acetylglucosamine modification is an important post-translational modification, emerging as a novel regulatory mechanism in various cellular events. Recently, several studies have shown that O-GlcNAcylation plays an essential role in human breast, lung, and colon cancers. With regard to skin cancers, the role of O-GlcNAcylation has yet to be elucidated. To investigate whether O-GlcNAcylation is linked to human skin tumor development, immunohistochemical analysis was performed to investigate the presence of OGlcNAcylation in various skin tumors. We evaluated the levels of O-GlcNAcylation, O-GlcNAc transferase, and O-GlcNAcase in 29 benign tumors, 12 premalignant tumors, and 26 malignant tumors in skin. Compared to the benign tumors, premalignant and malignant tumors had increased patterns of O-GlcNAcylation. In addition, the O-GlcNAc transferase and O-GlcNAcase levels were higher in premalignant and malignant tumors than in benign tumors. Interestingly, O-GlcNAcase levels were significantly increased in premalignant tumors compared to benign and malignant tumors. These results suggest that O-GlcNAcylation of proteins may play an important role in the development of human skin tumors.
ScienceON
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