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 4

Loss of miR-378 in BAT impairs angiogenesis and delays wound healing.

Options: View larger image (or click on image) Download as PowerPoint
Loss of miR-378 in BAT impairs angiogenesis and delays wound healing. (A...
(A) Circled heatmap of miRNA-Seq from BAT (GSE41306, left) and serum (right). Serum was pooled from 5 mice per group after 3-day cold exposure. (B) Expression levels of miRNA candidates in serum of mice kept at room temperature and 4°C (n = 3). (C) Schematic showing creation of miR-378Adipo KO mice. (D) miR-378a-3p expression levels in BAT, inguinal and epididymal WAT, liver, and muscle of control and miR-378Adipo-KO mice (n = 4–6). (E) Bar chart illustrates relative abundance of miR-378 across different adipose depots, including BAT and inguinal and epididymal WAT. (F) qPCR was used to validate miR-378a-3p level in serum of miR-378Adipo–KO mice (n = 3–4). (G) CD31 staining of wounds from the miR-378Adipo-KO and littermate control mice. Quantification of CD31 relative area is shown on the right (n = 3). Scale bar: 500 μm (top) and 100 μm (bottom). (H) Representative images of wounds of control and miR-378Adipo-KO mice. (I) Quantitative analysis of the wound closure rate of control and miR-378Adipo-KO mice (n = 3). (J) Representative images of blood flow at the wounds in miR-378Adipo-KO mice and control mice. The calculated wound microvascular perfusion is shown on the right (n = 3). (K) Representative images of Evans blue staining of injured femoral artery in control mice, miR-378Adipo-KO mice, and AAV-miR-378–treated miR-378Adipo-KO mice (n = 4). Quantification data of percentage of reendothelialization are shown on the right. The value n represents the number of biologically independent samples, from which all experimental data were obtained. Statistical analysis was performed using 2-tailed Student’s t test (B, D, F, G, I, and J) or 1-way ANOVA with Tukey’s multiple-comparison test (K). The data are expressed as mean ± SEM. NS = not significant, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.