Correlation Engine 2.0
Clear Search sequence regions


Sizes of these terms reflect their relevance to your search.

MT1-MMP (MMP14) is a collagenolytic enzyme located at the cell surface and implicated in extracellular matrix (ECM) remodeling. Mmp14(-/-) mice present dwarfism, bone abnormalities, and premature death. We demonstrate herein that the loss of MT1-MMP also causes cardiac defects and severe metabolic changes, and alters the cytoskeleton and the nuclear lamina structure. Moreover, the absence of MT1-MMP induces a senescent phenotype characterized by up-regulation of p16(INK4a) and p21(CIP1/WAF) (1), increased activity of senescence-associated β-galactosidase, generation of a senescence-associated secretory phenotype, and somatotroph axis alterations. Consistent with the role of retinoic acid signaling in nuclear lamina stabilization, treatment of Mmp14(-/-) mice with all-trans retinoic acid reversed the nuclear lamina alterations, partially rescued the cell senescence phenotypes, ameliorated the pathological defects in bone, skin, and heart, and extended their life span. These results demonstrate that nuclear architecture and cell senescence can be modulated by a membrane protease, in a process involving the ECM as a key regulator of nuclear stiffness under cell stress conditions. © 2015 The Authors.

Citation

Ana Gutiérrez-Fernández, Clara Soria-Valles, Fernando G Osorio, Jesús Gutiérrez-Abril, Cecilia Garabaya, Alina Aguirre, Antonio Fueyo, María Soledad Fernández-García, Xose S Puente, Carlos López-Otín. Loss of MT1-MMP causes cell senescence and nuclear defects which can be reversed by retinoic acid. The EMBO journal. 2015 Jul 14;34(14):1875-88

Expand section icon Mesh Tags

Expand section icon Substances


PMID: 25991604

View Full Text