Synechococcus elongatus PCC7942 secretes extracellular vesicles to accelerate cutaneous wound healing by promoting angiogenesis

被引：88

作者：

Yin, Hao ^{[1
,2
]}

Chen, Chun-Yuan ^{[1
,2
]}

Liu, Yi-Wei ^{[2
,3
]}

Tan, Yi-Juan ^{[2
]}

Deng, Zhi-Li ^{[4
,8
]}

Yang, Fei ^{[7
]}

Huang, Fei-Yu ^{[7
]}

Wen, Cong ^{[7
]}

Rao, Shan-Shan ^{[2
,9
]}

Luo, Ming-Jie ^{[2
,9
]}

Hu, Xiong-Ke ^{[2
]}

Liu, Zheng-Zhao ^{[2
,3
,4
,6
]}

Wang, Zhen-Xing ^{[2
]}

Cao, Jia ^{[2
]}

Liu, Hao-Ming ^{[2
]}

Liu, Jiang-Hua ^{[1
,2
]}

Yue, Tao ^{[1
,2
]}

Tang, Si-Yuan ^{[9
]}

Xie, Hui ^{[1
,2
,3
,4
,5
,6
]}

机构：

[1] Cent S Univ, Xiangya Hosp, Dept Orthoped, Changsha 410008, Hunan, Peoples R China

[2] Cent S Univ, Xiangya Hosp, Movement Syst Injury & Repair Res Ctr, Changsha 410008, Hunan, Peoples R China

[3] Cent S Univ, Xiangya Hosp, Dept Sports Med, Changsha 410008, Hunan, Peoples R China

[4] Hunan Key Lab Organ Injury Aging & Regenerat Med, Changsha 410008, Hunan, Peoples R China

[5] Hunan Key Lab Bone Joint Degenerat & Injury, Changsha 410008, Hunan, Peoples R China

[6] Cent S Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha 410008, Hunan, Peoples R China

[7] Cent S Univ, Xiangya Sch Publ Hlth, Dept Occupat & Environm Hlth, Changsha 410078, Hunan, Peoples R China

[8] Cent S Univ, Xiangya Hosp, Dept Dermatol, Changsha 410008, Hunan, Peoples R China

[9] Cent S Univ, Xiangya Nursing Sch, Changsha 410013, Hunan, Peoples R China

来源：

THERANOSTICS | 2019年 / 9卷 / 09期

基金：

中国国家自然科学基金; 中国博士后科学基金;

关键词：

Synechococcus elongatus PCC 7942; extracellular vesicles; wound healing; angiogenesis; OUTER-MEMBRANE VESICLES; CELLS; EXOSOMES;

D O I：

10.7150/thno.31884

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

100103 [病原生物学]; 100218 [急诊医学];

摘要：

Poor wound healing affects millions of people worldwide each year and needs better therapeutic strategies. Synechococcus elongatus PCC 7942 is a naturally occurring photoautotrophic cyanobacterium that can be easily obtained and large-scale expanded. Here, we investigated the therapeutic efficacy of this cyanobacterium in a mouse model of acute burn injury and whether the secretion of extracellular vesicles (EVs), important mediators of cell paracrine activity, is a key mechanism of the cyanobacterium-induced regulation of wound healing. Methods: The effects of Synechococcus elongatus PCC 7942 on burn wound healing in mice under light or dark conditions were evaluated by measuring wound closure rates, histological and immunofluorescence analyses. A series of assays in vivo and in vitro were conducted to assess the impact of the cyanobacterium on angiogenesis. GW4869 was used to interfere with the secretion of EVs by the cyanobacterium and the abilities of the GW4869-pretreated and untreated Synechococcus elongatus PCC 7942 to regulate endothelial angiogenesis were compared. The direct effects of the cyanobacterium-derived EVs (S. elongatus-EVs) on angiogenesis, wound healing and expressions of a class of pro-inflammatory factors that have regulatory roles in wound healing were also examined. Results: Synechococcus elongatus PCC 7942 treatment under light and dark conditions both significantly promoted angiogenesis and burn wound repair in mice. In vitro, the cyanobacterium enhanced angiogenic activities of endothelial cells, but the effects were markedly blocked by GW4869 pretreatment. S. elongatus-EVs were capable of augmenting endothelial angiogenesis in vitro, and stimulating new blood vessel formation and burn wound healing in mice. The expression of interleukin 6 (IL-6), which has an essential role in angiogenesis during skin wound repair, was induced in wound tissues and wound healing-related cells by S. elongatus-EVs and Synechococcus elongatus PCC 7942. Conclusion: Synechococcus elongatus PCC 7942 has the potential as a promising strategy for therapeutic angiogenesis and wound healing primarily by the delivery of functional EVs, not by its photosynthetic activity. The promotion of IL-6 expression may be a mechanism of the cyanobacterium and its EVs-induced pro-angiogenic and -wound healing effects.

引用

页码：2678 / 2693

页数：16

共 37 条

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