Cardiovascular-Program, Institut de Recerca Sant Pau, IIB-Sant Pau, 08025 Barcelona, Spain.
Ciber CV, Instituto Carlos III, 28029 Madrid, Spain.
Cells. 2024 Mar 14;13(6):513. doi: 10.3390/cells13060513.
The development of obesity is associated with substantial modulation of adipose tissue (AT) structure. The plasticity of the AT is reflected by its remarkable ability to expand or reduce in size throughout the adult lifespan, which is linked to the development of its vasculature. This increase in AT vasculature could be mediated by the differentiation of adipose tissue-derived stem cells (ASCs) into endothelial cells (ECs) and form new microvasculature. We have already shown that microRNA (miRNA)-145 regulates the differentiation of ASCs into EC-like (ECL) cells. Here, we investigated whether ASCs-differentiation into ECs is governed by a miRNAs signature that depends on fat depot location and /or the metabolic condition produced by obesity. Human ASCs, which were obtained from white AT by surgical procedures from lean and obese patients, were induced to differentiate into ECL cells. We have identified that miRNA-29b-3p in both subcutaneous (s)ASCs and visceral ASCs and miRNA-424-5p and miRNA-378a-3p in subcutaneous (s)ASCs are involved in differentiation into EC-like cells. These miRNAs modulate their pro-angiogenic effects on ASCs by targeting , , , and , and the MAPK signaling pathway. We show for the first time that miRNA-29b-3p upregulation contributes to ASCs' differentiation into ECL cells by directly targeting in both sASCs and visceral ASCs. Moreover, our results reveal that, independent of sASCs' origin (obese/lean), the upregulation of miRNA-378a-3p and the downregulation of miRNA-424-5p inhibit and overexpress and , respectively. In summary, both the adipose depot location and obesity affect the differentiation of resident ASCs through the expression of specific miRNAs.
肥胖的发展与脂肪组织（AT）结构的大量调节有关。AT 的可塑性反映在其在整个成年期内扩大或缩小的大小的显著能力上，这与它的血管系统的发展有关。AT 血管系统的增加可能是由脂肪组织衍生的干细胞（ASCs）分化为内皮细胞（ECs）并形成新的微血管来介导的。我们已经表明，微小 RNA（miRNA）-145 调节 ASCs 分化为内皮细胞样（ECL）细胞。在这里，我们研究了 ASCs 分化为 ECs 是否受 miRNA 特征的控制，该特征取决于脂肪库的位置和/或肥胖引起的代谢状况。通过手术从瘦人和肥胖患者的白色 AT 中获得的人 ASCs 被诱导分化为 ECL 细胞。我们已经确定，皮下（s）ASCs 和内脏 ASCs 中的 miRNA-29b-3p 以及皮下（s）ASCs 中的 miRNA-424-5p 和 miRNA-378a-3p 参与分化为内皮细胞样细胞。这些 miRNA 通过靶向 、 、 、 和 MAPK 信号通路来调节它们对 ASCs 的促血管生成作用。我们首次表明，miRNA-29b-3p 的上调通过直接靶向 sASCs 和内脏 ASCs 中的 有助于 ASCs 分化为 ECL 细胞。此外，我们的结果表明，独立于 sASCs 的起源（肥胖/瘦），miRNA-378a-3p 的上调和 miRNA-424-5p 的下调分别抑制 和过表达 和 。总之，脂肪库的位置和肥胖通过表达特定的 miRNA 影响驻留 ASCs 的分化。
