Carrillo-Gálvez, Ana BelénGálvez-Peisl, SheylaGonzález-Correa, Juan Elíasde Haro-Carrillo, MarinaAyllón, VerónicaCarmona-Sáez, PedroRamos-Mejía, VerónicaGalindo-Moreno, PabloCara, Francisca E.Granados-Principal, SergioMuñoz, PilarMartin, FranciscoAnderson, Per2022-03-312022-03-312020Carrillo-Gálvez AB, Gálvez-Peisl S, González-Correa JE, de Haro-Carrillo M, Ayllón V, Carmona-Sáez P, et al. GARP is a key molecule for mesenchymal stromal cell responses to TGF-β and fundamental to control mitochondrial ROS levels. Stem Cells Transl Med. 2020 May;9(5):636-6502157-6564http://hdl.handle.net/10668/3512Multipotent mesenchymal stromal cells (MSCs) have emerged as a promising cell therapy in regenerative medicine and for autoimmune/inflammatory diseases. However, a main hurdle for MSCs-based therapies is the loss of their proliferative potential in vitro. Here we report that glycoprotein A repetitions predominant (GARP) is required for the proliferation and survival of adipose-derived MSCs (ASCs) via its regulation of transforming growth factor-β (TGF-β) activation. Silencing of GARP in human ASCs increased their activation of TGF-β which augmented the levels of mitochondrial reactive oxygen species (mtROS), resulting in DNA damage, a block in proliferation and apoptosis. Inhibition of TGF-β signaling reduced the levels of mtROS and DNA damage and restored the ability of GARP-/low ASCs to proliferate. In contrast, overexpression of GARP in ASCs increased their proliferative capacity and rendered them more resistant to etoposide-induced DNA damage and apoptosis, in a TGF-β-dependent manner. In summary, our data show that the presence or absence of GARP on ASCs gives rise to distinct TGF-β responses with diametrically opposing effects on ASC proliferation and survival.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/DNA damageMesenchymal stromal cells (MSCs)ProliferationROSTGF-βDaño del ADNCélulas madre mesenquimatosasProliferación celularEspecies reactivas de oxígenoFactor de crecimiento transformador betaMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Anatomy::Cells::Stem Cells::Multipotent Stem Cells::Mesenchymal Stromal CellsMedical Subject Headings::Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Organelles::MitochondriaMedical Subject Headings::Chemicals and Drugs::Inorganic Chemicals::Free Radicals::Reactive Oxygen SpeciesMedical Subject Headings::Chemicals and Drugs::Biological Factors::Intercellular Signaling Peptides and Proteins::Transforming Growth Factors::Transforming Growth Factor betaresearch article32073751open access10.1002/sctm.19-03722157-6580PMC7180295