长链非编码RNA-CASC2通过TGF-β/Smad通路调节成纤维细胞在瘢痕疙瘩中的作用及分子机制研究

Keloid is a benign collagen proliferative disease secondary to skin injury. Its prevention and treatment remain challenges in dermatology and plastic surgery. The pathogenesis of keloid remains unknown and human keloid fibroblasts(HKFs) play a major role in its pathogenesis. Cancer susceptibility candidate2 (CASC2) belongs to lncRNA family and plays tumor suppresive role in several human malignancies. Our previous research performwed lncRNA sequencing and indicated that CASC2 was downregulated in keloid tissue compared with normal skin. In addtion, RT-qPCR confirmed its downregulation in keloid tissue. Morevover, CASC2 inhibited cell proliferation and invasion of HKF. CASC2 could inhibit the expression of Smad. So we proposed the scientific hypothesis that "CASC2 regulates the function of HKF through TGF-β/smad pathway and inhibits the development of keloid ". The present project plans to investigate the role of CASC2 in the proliferation, invasion, metastasis, autophagy and collagen synthesis of HKF, as well as its role in nude mouse model of keloid. Morever, we also try to elucidate the underlying molecular mechanism of CASC2 in the pathogenesis of keloid. This study may contribute to the understanding of the etiology and pathogeneisis of keloid.

瘢痕疙瘩是继发于皮肤损伤的一种胶原性过度沉积的疾病，其防治一直是皮肤科及整形外科的挑战。瘢痕疙瘩发病机制不明，瘢痕疙瘩成纤维细胞（human keloid fibrobast,HKF）在其中占据主要作用。Cancer susceptibility candidate2(CASC2)属于lncRNA，可抑制多种肿瘤发生发展。我们前期通过对瘢痕疙瘩行LncRNA测序，发现CASC2在瘢痕疙瘩组织中表达明显降低，并通过RT-qPCR扩大样本证实其表达降低，CASC2抑制HKF的增殖及侵袭，并可抑制Smad的表达，故提出科学假说“CASC2通过TGF-β/smad通路调节HKF的功能抑制瘢痕疙瘩的发生发展”。本课题计划通过细胞功能实验及瘢痕疙瘩裸鼠模型，检测CASC2对HKF增殖、迁移、凋亡、自噬及胶原合成的影响，并研究其下游信号通路，为阐明瘢痕疙瘩的发病机制提供依据。

瘢痕疙瘩是继发于皮肤损伤的一种胶原性过度沉积的疾病，其防治一直是皮肤科及整形外科的挑战。瘢痕疙瘩发病机制不明，瘢痕疙瘩成纤维细胞（human keloid fibrobast,HKF）在其中占据主要作用。Cancer susceptibility candidate2(CASC2)属于lncRNA，可抑制多种肿瘤发生发展。我们前期通过对瘢痕疙瘩行LncRNA测序，发现CASC2在瘢痕疙瘩组织中表达明显降低，并通过RT-qPCR扩大样本证实其表达降低，CASC2抑制HKF的增殖及侵袭，并可抑制Smad的表达，故提出科学假说“CASC2通过TGF-β/smad通路调节HKF的功能抑制瘢痕疙瘩的发生发展”。本课题计划通过细胞功能实验及瘢痕疙瘩裸鼠模型，检测CASC2对HKF增殖、迁移、凋亡、自噬及胶原合成的影响，并研究其下游信号通路，为阐明瘢痕疙瘩的发病机制提供依据。