The MSC-Derived Exosomal lncRNA H19 Promotes Wound Healing in Diabetic Foot Ulcers by Upregulating PTEN via MicroRNA-152-3p

被引：222

作者：

Li, Bo ^{[1
]}

Luan, Song ^{[2
]}

Chen, Jing ^{[2
]}

Zhou, Yue ^{[2
]}

Wang, Tingting ^{[2
]}

Li, Zhijuan ^{[2
]}

Fu, Yili ^{[3
]}

Zhai, Aixia ^{[4
]}

Bi, Changlong ^{[5
]}

机构：

[1] Harbin Med Univ, Affiliated Hosp 4, Dept Endocrinol, Harbin 150001, Peoples R China

[2] Harbin Med Univ, Affiliated Hosp 4, Dept Gen 2, Harbin 150001, Peoples R China

[3] Harbin Inst Technol, Sch Life Sci & Technol, Harbin 150001, Peoples R China

[4] Harbin Med Univ, Dept Microbiol, 157 Baojian Rd, Harbin 150081, Heilongjiang, Peoples R China

[5] Sun Yat Sen Univ, Affiliated Hosp 8, Dept Endocrinol, 3025 Shennan Middle Rd, Shenzhen 518033, Guangdong, Peoples R China

来源：

MOLECULAR THERAPY-NUCLEIC ACIDS | 2020年 / 19卷

基金：

中国国家自然科学基金;

关键词：

MESENCHYMAL STEM-CELLS; COMPETING ENDOGENOUS RNA; EXPRESSION; BIOMARKERS; MIRNA;

D O I：

10.1016/j.omtn.2019.11.034

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Mesenchymal stem cells (MSCs) have been reported to hold promise to accelerate the wound-healing process in diabetic foot ulcer (DFU) due to the multilineage differentiation potential. Hence, this study intended to explore the wound healing role of MSC-derived exosomes containing long noncoding RNA (lncRNA) H19 in DFU. lncRNA H19 was predicated to bind to microRNA-152-3p (miR-152-3p), which targeted phosphatase and tensin homolog (PTEN) deleted on chromosome ten. Fibroblasts in DFU samples exhibited highly expressed miR-152-3p and poorly expressed lncRNA H19 and PTEN, along with an activated phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (Akt1) signaling pathway. The fibroblasts were cocultured with lncRNA H19-transfected MSCs and MSC-derived exosomes to assess the effect of the lncRNA H19/miR-152-3p/PTEN axis on the biological activities and inflammation in fibroblasts. Mouse models of DFU were developed by streptozotocin, which was injected with MSC-derived exosomes overexpressing lncRNA H19. lncRNA H19 in MSCs was transferred through exosomes to fibroblasts, the mechanism of which improved wound healing in DFU, corresponded to promoted fibroblast proliferation and migration, as well as suppressed apoptosis and inflammation. Wound healing in mice with DFU was facilitated following the injection of MSC-derived exosomes overexpressing lncRNA H19. Taken together, MSC-derived exosomal lncRNA H19 prevented the apoptosis and inflammation of fibroblasts by impairing miR-152-3p-mediated PTEN inhibition, leading to the stimulated wound-healing process in DFU.

引用

页码：814 / 826

页数：13

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