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Exosomes of adipose-tissue-derived stem cells over-expressing Neat1 promote wound healing by sponging miR-17-5p and inducing autophagy protein Ulk1

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机构： [1]Department of Plastic Surgery, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing, 100191, China. [2]MOE Laboratory of Biosystem Homeostasis and Protection and Life Sciences Institute, Zhejiang University, Hangzhou, 310058, China. [3]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, 610041, China.

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Wound healing undergoes intricate phases: hemostasis, inflammation, proliferation and remodeling. Stem cell therapy based on adipose-tissue-derived stem cells (ADSCs) exosomes is considered as potential effective treatment for accelerating wound healing. While the molecular mechanisms of wound healing using ADSCs-exo remain largely unknown.Circular wounds of 1 × 1 cm were generated on C57BL/6 mice, followed by oricell C57BL/6 mouse adipose-derived mesenchymal stem cell suspension treatment, and wound area was measured and recorded at day 0, day 7 and day 21 respectively. A comprehensive transcriptome profiling of skin wounds was conducted in the mouse model. Importantly, we also examined autophagy and cell migration in mouse keratinocytes treated with ADSCs exosomes. Further competing endogenous RNA (ceRNA) networks were also used to reveal the relationship between Neat1 and Ulk1.Mouse keratinocytes treated with ADSCs exosomes showed significant up-regulation of pathways related to wound-healing, including response to virus, bacterium, immune system and wounding. Activated autophagy was detected, which significantly promote the wounds repair of mice. ceRNA networks uncovered that Neat1 induces the expression of Ulk1 and thus up-regulates autophagic activity to promote wound repair through sponging miR-17-5p.Collectively, these results reveal a novel molecular mechanism that the autophagy pathway enhanced by Neat1/miR-17-5p/Ulk1 axis can promote the wound-healing and suggest that lncRNA Neat1 loaded by ADSCs-exo might be a potential therapeutic target for skin no-healing wounds.Copyright © 2022 by the American Society of Plastic Surgeons.

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出版当年[2022]版：

大类 | 1 区

医学

小类 | 1 区外科

最新[2023]版：

大类 | 2 区

医学

小类 | 2 区外科

第一作者：

第一作者机构： [1]Department of Plastic Surgery, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing, 100191, China. [*1]Department of Plastic Surgery, Peking University Third Hospital 49 North Garden Rd. Beijing, China

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通讯机构： [1]Department of Plastic Surgery, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing, 100191, China. [3]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, 610041, China. [*1]Department of Plastic Surgery, Peking University Third Hospital 49 North Garden Rd. Beijing, China [*2]Department of Plastic Surgery, Peking University Third Hospital 49 North Garden Rd. Beijing, China [*3]BS State Key Laboratory of Biotherapy and Cancer Center, West China Hospital 37 Guoxue Alley Chengdu, China

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