胰岛素样生长因子 2 通过 IGF-1R 和 IR 调节大鼠脂肪间充质干细胞的增殖和分化。

Insulin-like growth factor 2 regulates the proliferation and differentiation of rat adipose-derived stromal cells via IGF-1R and IR.

机构信息

Department of Pediatric Intensive Care Unit, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, 400014 China; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, 400014 China; Chongqing Engineering Research Center of Stem Cell Therapy, Children's Hospital of Chongqing Medical University, Chongqing, China.

State Key Lab of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing 400042, China.

出版信息

Cytotherapy. 2019 Jun;21(6):619-630. doi: 10.1016/j.jcyt.2018.11.010. Epub 2019 Apr 5.

DOI:10.1016/j.jcyt.2018.11.010

PMID:30956007

Abstract

BACKGROUND

Insulin-like growth factor 2 (IGF2), an essential component of the stem cell niche, has been reported to modulate the proliferation and differentiation of stem cells. Previously, a continuous expression of IGF2 in tissues was reported to maintain the self-renewal ability of several types of stem cells. Therefore, in this study, we investigated the expression of IGF2 in adipose tissues and explored the effects of IGF2 on adipose-derived stromal cells (ADSCs) in vitro.

METHODS

The expression pattern of IGF2 in rat adipose tissues was determined by gene expression and protein analyses. The effect of IGF2 on proliferation, stemness-related marker expression and adipogenic and osteogenic differentiation was systematically investigated. Furthermore, antagonists of IGF2-specific receptors-namely, BMS-754807 and picropodophyllin-were added to explore the underlying signal transduction mechanisms.

RESULTS

IGF2 levels displayed a tendency to decrease with age in rat adipose tissues. After the addition of IGF2, isolated ADSCs displayed higher proliferation and expression of the stemness-related markers NANOG, OCT4 and SOX2 and greater differentiation potential to adipocytes and osteoblasts. Additionally, both type 1 insulin-like growth factor receptor (IGF-1R) and insulin receptor (IR) participated in the IGF2-mediated promotion of stemness in ADSCs.

CONCLUSIONS

Our findings indicate that IGF2 could enhance the stemness of rat ADSCs via IGF-1R and IR and may highlight an effective method for the expansion of ADSCs for clinical application.

摘要

背景

胰岛素样生长因子 2（IGF2）是干细胞生态位的重要组成部分，据报道其可以调节干细胞的增殖和分化。先前有报道称，IGF2 在组织中的持续表达可以维持多种类型干细胞的自我更新能力。因此，在这项研究中，我们检测了 IGF2 在脂肪组织中的表达，并探讨了 IGF2 对脂肪来源的基质细胞（ADSCs）的体外作用。

方法

通过基因表达和蛋白分析确定 IGF2 在大鼠脂肪组织中的表达模式。系统研究了 IGF2 对细胞增殖、干细胞相关标志物表达以及成脂和成骨分化的影响。此外，还添加了 IGF2 特异性受体拮抗剂-BMS-754807 和 picropodophyllin-以探讨潜在的信号转导机制。

结果

IGF2 水平在大鼠脂肪组织中随年龄的增长呈下降趋势。添加 IGF2 后，分离的 ADSCs 表现出更高的增殖能力和更高的干细胞相关标志物 NANOG、OCT4 和 SOX2 的表达水平，并且向脂肪细胞和成骨细胞分化的潜力更大。此外，IGF-1R 和胰岛素受体（IR）均参与了 IGF2 介导的 ADSCs 中干细胞特性的促进作用。