BAT-derived miR-378a-3p facilitates endothelial angiogenic function and promotes wound healing
Hongyan Deng, Yuyu Xie, Jiadai Liu, Jing Ge, Qianqian Kang, Rui He, Zhihan Wang, Xuemin Peng, Zengzhe Zhu, Wenshe Wang, Yulian Liu, Ronghui Gao, Ruping Pan, Min Yang, Yong Chen
Hongyan Deng, Yuyu Xie, Jiadai Liu, Jing Ge, Qianqian Kang, Rui He, Zhihan Wang, Xuemin Peng, Zengzhe Zhu, Wenshe Wang, Yulian Liu, Ronghui Gao, Ruping Pan, Min Yang, Yong Chen
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Research Article Metabolism Vascular biology

BAT-derived miR-378a-3p facilitates endothelial angiogenic function and promotes wound healing

Abstract

Interscapular brown adipose tissue (BAT), one of the most vascularized tissues in the body, exemplifies the intricate crosstalk between the vascular system and adipocytes. BAT is known to secrete abundant exosomes into circulation, and exosomes are known to play a key role in vascular remodeling and cell migration. However, whether BAT-derived exosomes (BATexos) modulate peripheral vasculature remains unclear. Here, we report that BATexos promoted peripheral angiogenesis and vascular repair. Among their cargo, miR-378a-3p was highly enriched and identified as a key mediator of endothelial angiogenic function. The overexpression of miR-378a-3p in endothelial cells substantially promoted cell migration and tube formation. Conversely, inhibition of exosome secretion from BAT impaired vascular repair and delayed wound healing. Mechanistically, miR-378a-3p directly targeted the phosphatase and tensin homolog (Pten), thereby activating the PI3K/AKT signaling pathway. Liposomes encapsulating miR-378 mimics promoted angiogenesis and accelerated wound healing in a diabetic mouse model. Collectively, this study uncovers BAT-derived miR-378a-3p as a key regulator of vessel regeneration and tissue repair after injury, offering therapeutic potential for treating vascular complications in metabolic disease.

Authors

Hongyan Deng, Yuyu Xie, Jiadai Liu, Jing Ge, Qianqian Kang, Rui He, Zhihan Wang, Xuemin Peng, Zengzhe Zhu, Wenshe Wang, Yulian Liu, Ronghui Gao, Ruping Pan, Min Yang, Yong Chen

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Figure 2

BATexos facilitate vascular repair and wound healing.

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BATexos facilitate vascular repair and wound healing. (A) Schematic diag...
(A) Schematic diagram of BAT with GW4869/control vehicle injection in WT mice or BATexos/PBS treatment in BATectomy mice. (B) Morphological characteristics of BATexos under a transmission electron microscope. Scale bar: 100 nm. (C) The diameter of the BATexo particles was investigated via nanoparticle tracking analysis. (D) Western blot analysis of specific marker proteins (CD63 and TSG101) for exosomes in the serum of mice kept at room temperature or cold (at 4°C). (E) Evans blue staining and quantitative analysis of the femoral artery in WT mice injected with GW4869 in BAT or BATectomy mice injected with BATexos via the tail vein. (F) Immunofluorescence staining for CD31 (red) in the wound and quantitative analysis in mice treated with GW4869 or BATexos (n = 3–4). Scale bar: 50 μm. (G) Representative images of skin wounds in the GW4869/vehicle-treated WT mice and BATexos/PBS-treated BATectomy mice. Quantification of wound closure rate presented as a line graph on the right. (H) Representative images of blood flow at the wounds in vehicle/GW4869-treated WT mice and PBS/BATexos-treated BATectomy mice. The calculated wound microvascular perfusion is shown on the right (n = 3–4). The value n represents the number of biologically independent samples, from which all experimental data were obtained. Statistical significance was assessed by 2-tailed Student’s t test. The data are expressed as mean ± SEM. *P < 0.05, **P < 0.01, ****P < 0.0001.