CD133与相关信号通路在胆脂瘤形成中的作用

In most of clinical specimens，the CD133 high expression in human cholesteatoma keratinocytes cell with Id1 and NF-κB expression. According to the new finding of the preliminary study, we put forward a new hypothesis that chronic otitis media may increase the activity of Id1 and NF-κB, which in turn promote keratinocyte expression of CD133 cell marker, then obtain self-renewal capacity and become cholesteatoma seed cell populations. To develop an in vitro model, we use of Human keratinocytes cell line (Rhek-1A) and transfection of Id1 and NF-κB to Rhek-1A cells, to compare the expression of CD133 for these cell lines, and to explore the effects of Id1 and NF-κB on the expression of CD133,cell self-renewal capacity, proliferation and differentiation, anti-apoptotic and its signaling pathways. Sorting of CD133-positive cells were inoculated into nude mouse ear bubble, to investigate the effects of Id1,NF-κB and CD133 on the formation of cholesteatoma.The research will be important to further understand the pathogenesis of cholesteatoma.

申请者前期研究发现，临床胆脂瘤标本的角化上皮细胞CD133高表达伴有Id1和NF-κB高表达的现象，据此提出慢性中耳炎症，可能通过调高Id1和NF-κB的活性，促进角化上皮高表达CD133等标志，获得自我更新能力，成为胆脂瘤种子细胞的新假说。本课题利用人角化上皮Rhek-1A细胞转染Id1和NF-κB建立的细胞系，比较这些细胞系中CD133表达的差异，探讨Id1和NF-κB对CD133表达和细胞自我更新、增殖分化、抗凋亡及其信号通路的影响；分选CD133阳性、适度分化的细胞作为"种子"细胞，接种裸鼠耳泡，并将形成的"胆脂瘤"与临床胆脂瘤标本进行比对，验证Id1、NF-κB和 CD133对胆脂瘤形成的影响。研究结果对进一步了解胆脂瘤发病机制，具有重要意义。