Differentiation of Adipose Tissue Mesenchymal Stem Cells into Endothelial Cells Depends on Fat Depot Conditions: Regulation by miRNA
Por:
Arderiu, G, Civit-Urgell, A, Diez-Caballero, A, Moscatiello, F, Ballesta, C, Badimon, L
Publicada:
1 mar 2024
Resumen:
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 FGFR1, NRP2, MAPK1, and TGF-beta 2, 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 TGFB2 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 MAPK1 and overexpress FGFR1 and NRP2, respectively. In summary, both the adipose depot location and obesity affect the differentiation of resident ASCs through the expression of specific miRNAs.
Filiaciones:
Arderiu, G:
IIB St Pau, Inst Recerca St Pau, Cardiovasc Program, Barcelona 08025, Spain
Inst Carlos III, Ciber CV, Madrid 28029, Spain
Civit-Urgell, A:
IIB St Pau, Inst Recerca St Pau, Cardiovasc Program, Barcelona 08025, Spain
Univ Barcelona UB, Fac Pharm & Food Sci, Barcelona 08028, Spain
Diez-Caballero, A:
Grp Quiron Salut, Ctr Med Teknon, Barcelona 08022, Spain
Moscatiello, F:
Grp Quiron Salut, Ctr Med Teknon, Barcelona 08022, Spain
Ballesta, C:
Grp Quiron Salut, Ctr Med Teknon, Barcelona 08022, Spain
Badimon, L:
IIB St Pau, Inst Recerca St Pau, Cardiovasc Program, Barcelona 08025, Spain
Inst Carlos III, Ciber CV, Madrid 28029, Spain
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