Tian Yi, Jin Lan, Zhang Wenhong, Ya Zumeng, Cheng Yuan, Zhao Hongyun
Department of Plastic Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
Department of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
Genes Dis. 2018 May 18;6(2):185-192. doi: 10.1016/j.gendis.2018.05.002. eCollection 2019 Jun.
A keloid (KD) is a benign dermal fibrotic tumor. Treatment of KDs is challenging and the recurrence rate is high; thus, there is an unmet need to explore new target sites and new treatment methods. As a tumor-associated cytokine, autocrine motility factor (AMF) can effectively stimulate the random and directional movement of cells. We first found that AMF was overexpressed in keloid fibroblasts (KFs) and the proliferation and migration of KFs were promoted by AMF stimulation. After treatment with Y-27632, RhoA kinase inhibitor, the proliferation and migration capacity of KFs declined significantly, and type I collagen protein, active RhoA and ROCK1 also were downregulated. In addition, a KD transplantation model was established under the skin of nude mice, with KD intramural injection AMF siRNA, we found that the weight of the KD was smaller than in the control group ( < 0.05), KD tissue sections stained by HE and Masson showed that fibers became loose and the blood vessels were visibly reduced. In conclusion, AMF siRNA is expected to be a novel strategy to treat KD by inhibiting signaling pathway of RhoA/ROCK1.
瘢痕疙瘩(KD)是一种良性真皮纤维化肿瘤。KD的治疗具有挑战性且复发率高;因此,探索新的靶点和新的治疗方法存在未满足的需求。作为一种肿瘤相关细胞因子,自分泌运动因子(AMF)能有效刺激细胞的随机和定向运动。我们首次发现AMF在瘢痕疙瘩成纤维细胞(KF)中过表达,且AMF刺激可促进KF的增殖和迁移。用RhoA激酶抑制剂Y-27632处理后,KF的增殖和迁移能力显著下降,I型胶原蛋白、活性RhoA和ROCK1也下调。此外,在裸鼠皮下建立KD移植模型,向KD壁内注射AMF siRNA,我们发现KD的重量比对照组小(<0.05),HE和Masson染色的KD组织切片显示纤维变得疏松,血管明显减少。总之,AMF siRNA有望通过抑制RhoA/ROCK1信号通路成为治疗KD的新策略。