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
View: Text | PDF
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

×

Figure 7

Liposome-encapsulated miR-378 mimics promote wound healing in diabetic mice.

Options: View larger image (or click on image) Download as PowerPoint
Liposome-encapsulated miR-378 mimics promote wound healing in diabetic m...
(A) Random blood glucose in diabetic (DM) and nondiabetic (NDM) mouse wounds. (B) Relative expression level of miR-378 in DM and NDM mouse wounds. (C) CD31 staining of DM and NDM wounds. Scale bar: 200 μm. Quantification of CD31 relative area is shown on the right (n = 4). (D) Representative images of DM and NDM wounds. (E) Quantitative analysis of wound healing rates in DM and NDM groups. (F) Angiogenesis-related genes detected in wounds of DM and NDM mice. (G) Schematic illustration of the preparation of miR-378a-3p LNPs. (H) Schematic illustration of the DM wound model and treatment with miR-378 LNPs. (I) Relative miR-378 levels in DM wounds. (J) CD31 staining of DM wounds treated with miR-378 LNPs. Scale bar: 200 μm (top) and 50 μm (bottom). (K) Quantification of CD31 relative area in DM wounds treated with control or miR-378 LNPs (n = 4–5). (L) Representative images of DM wounds treated with miR-378 LNPs (n = 3). (M) Quantification of wound closure rate in mice treated with miR-378 LNPs (n = 3). 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 < 0.001, ****P < 0.0001.