%0 Journal Article
%A Carrillo-Gálvez, Ana Belén
%A Gálvez-Peisl, Sheyla
%A González-Correa, Juan Elías
%A de Haro-Carrillo, Marina
%A Ayllón, Verónica
%A Carmona-Sáez, Pedro
%A Ramos-Mejía, Verónica
%A Galindo-Moreno, Pablo
%A Cara, Francisca E.
%A Granados-Principal, Sergio
%A Muñoz, Pilar
%A Martin, Francisco
%A Anderson, Per
%T GARP is a key molecule for mesenchymal stromal cell responses to TGF-β and fundamental to control mitochondrial ROS levels
%D 2020
%@ 2157-6564
%U http://hdl.handle.net/10668/3512
%X Multipotent 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.
%K DNA damage
%K Mesenchymal stromal cells (MSCs)
%K Proliferation
%K ROS
%K TGF-β
%K Daño del ADN
%K Células madre mesenquimatosas
%K Proliferación celular
%K Especies reactivas de oxígeno
%K Factor de crecimiento transformador beta
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