RT Journal Article
T1 GARP is a key molecule for mesenchymal stromal cell responses to TGF-β and fundamental to control mitochondrial ROS levels
A1 Carrillo-Gálvez, Ana Belén
A1 Gálvez-Peisl, Sheyla
A1 González-Correa, Juan Elías
A1 de Haro-Carrillo, Marina
A1 Ayllón, Verónica
A1 Carmona-Sáez, Pedro
A1 Ramos-Mejía, Verónica
A1 Galindo-Moreno, Pablo
A1 Cara, Francisca E.
A1 Granados-Principal, Sergio
A1 Muñoz, Pilar
A1 Martin, Francisco
A1 Anderson, Per
K1 DNA damage
K1 Mesenchymal stromal cells (MSCs)
K1 Proliferation
K1 ROS
K1 TGF-β
K1 Daño del ADN
K1 Células madre mesenquimatosas
K1 Proliferación celular
K1 Especies reactivas de oxígeno
K1 Factor de crecimiento transformador beta
AB 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.
PB Wiley Periodicals, Inc. on behalf of AlphaMed Press
SN 2157-6564
YR 2020
FD 2020
LK http://hdl.handle.net/10668/3512
UL http://hdl.handle.net/10668/3512
LA en
NO Carrillo-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):636-650
DS RISalud
RD Apr 5, 2025