Shang Yong, Yu Dongmei, Hao Lijun
Plastic and Cosmetic Center, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Str. Nangang District, Harbin, 150001, People's Republic of China.
Cell Biochem Biophys. 2015 Jun;72(2):405-10. doi: 10.1007/s12013-014-0476-5.
Keloids, which possess invasive tumor-like behavior, have been clinically challenging to clinicians especially surgeons. Excessive extracellular matrix secreted from fibroblasts is the main histo-pathological feature of keloids. In this study, we transfected hTERT-siRNA into scar fibroblasts by liposome-adenoviral transduction in order to disrupt telomere length homeostasis and influence the cell cycle of fibroblasts. Our results showed that liposome hTERT-siRNA was able to knock down hTERT gene expression in scar fibroblasts. Moreover, the telomerase activity in hTERT-siRNA group was significantly reduced compared with the control groups. And the telomeric length of hTERT-siRNA group was significantly shortened as well. Further, flow cytometry studies and MTT assay demonstrated that apoptosis rate of fibroblasts in liposome hTERT-siRNA group significantly increased. These results indicated that the liposome-mediated hTERT gene transduction could inhibit the growth of fibroblasts in scar tissues suggesting a promising strategy of keloids treatment in the future.
瘢痕疙瘩具有侵袭性肿瘤样行为,对临床医生尤其是外科医生来说一直是个临床难题。成纤维细胞分泌过多的细胞外基质是瘢痕疙瘩的主要组织病理学特征。在本研究中,我们通过脂质体-腺病毒转导将hTERT-siRNA转染到瘢痕成纤维细胞中,以破坏端粒长度稳态并影响成纤维细胞的细胞周期。我们的结果表明,脂质体hTERT-siRNA能够敲低瘢痕成纤维细胞中hTERT基因的表达。此外,与对照组相比,hTERT-siRNA组的端粒酶活性显著降低。并且hTERT-siRNA组的端粒长度也显著缩短。进一步地,流式细胞术研究和MTT分析表明,脂质体hTERT-siRNA组成纤维细胞的凋亡率显著增加。这些结果表明,脂质体介导的hTERT基因转导可以抑制瘢痕组织中成纤维细胞的生长,这提示了未来治疗瘢痕疙瘩的一种有前景的策略。