LncRNA HULC promotes epithelial and smooth-muscle-like differentiation of adipose-derived stem cells by upregulation of BMP9
LncRNA HULC promotes epithelial and smooth-muscle-like differentiation of adipose-derived stem cells by upregulation of BMP9
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LncRNA HULC 通过上调 BMP9 促进脂肪干细胞的上皮和平滑肌样分化
DOI：
10.1691/ph.2018.7634
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发表时间：
2018-01-01
期刊：
影响因子：
1.6
通讯作者：
Wu, Jitao
中科院分区：
文献类型：
--
作者：
Li, Yongwei;Shan, Zhengfei;Wu, Jitao
目的：脂肪源性干细胞（ADSC）是间充质干细胞的来源，能够分化成许多细胞谱系，包括上皮细胞和平滑肌细胞。利用组织工程技术将脂肪干细胞用于尿道重建是最有前途的治疗方法。本研究旨在探讨IncRNA在肝癌（HULC）中高表达对ADSCs向上皮细胞和平滑肌样细胞分化的诱导作用。研究方法：从雄性狗中分离ADSC，并且通过用HULC表达载体慢病毒转染ADSC中的HULC表达来过表达。然后将转染的ADSC与5 μ M ATRA或2.5 ng/ml TGF-β 1和5 ng/ml PDGF-BB孵育21天。监测上皮分化和平滑肌样分化标志物的表达。此外，HULC和BMP 9在分化的上皮细胞和平滑肌样细胞中存在交叉调节。结果：HULC可提高ADSCs的细胞活力，但对ADSCs的凋亡无影响。HULC促进ADSC分化为上皮细胞和平滑肌样细胞，如Uroplakin-II、AE 1/AE 3、α-SMA、SM-MHC、钙调蛋白和SM-22 α的表达增加所证明。HULC对BMP 9有正向调节作用，而BMP 9沉默则抑制HULC对ADSC的诱导分化作用。HULC激活Wnt/beta-catenin通路，同时使Notch通路失活。结论：HULC通过BMP 9/Wnt/beta-catenin/Notch网络被证明是ADSC上皮和平滑肌样分化过程中的启动子。这项研究提供了第一个体外证据，表明基于HULC的治疗可能是一种有价值的方法，以促进尿道重建。
Aims: Adipose-derived stem cells (ADSCs), a source of mesenchymal stem cells, are able to differentiate into numerous cell lineages, including epithelial and smooth muscle cells. The use of ADSCs in tissue engineering technology has become the most promising therapeutic approach for urethral reconstruction. This study aimed to explore the effect of IncRNA highly upregulated in liver cancer (HULC) on the induction of ADSCs to differentiate into epithelial and smooth-muscle-like cells. Methods: ADSCs were isolated from a male dog, and the expression of HULC in ADSCs was overexpressed by transfection with HULC expressing vector lentivirus. The transfected ADSCs were then incubated with 5 mu M ATRA or 2.5 ng/ml TGF-beta 1 and 5 ng/ml PDGF-BB for 21 days. The expression of epithelial differentiation and smooth-muscle-like differentiation markers were monitored. Besides, cross-regulation between HULC and BMP9 was detected in the differentiated epithelial cells and smooth-muscle-like cells. Results: HULC increased cell viability of ADSCs, but has no impact on ADSCs apoptosis. HULC promotes ADSCs to differentiate into epithelial and smooth-muscle-like cells, as evidenced by the increases in the expression of Uroplakin-II, AE1/AE3, alpha-SMA, SM-MHC, Calponin, and SM-22 alpha. In addition, HULC could positively regulate BMP9, and BMP9 silence abolished HULC-promoted ADSC's differentiation. Furthermore, HULC activated Wnt/beta-catenin pathway while deactivated Notch pathway. Conclusion: HULC was demonstrated to be a promoter during the epithelial and smooth-muscle-like differentiation of ADSCs via the BMP9/Wnt/beta-catenin/Notch network. This study provides the first in vitro evidence that HULC-based therapy could be a valuable approach to promote urethral reconstruction.