Abstract:
:Cellular senescence is the permanent arrest of cell cycle, physiologically related to aging and aging-associated diseases. Senescence is also recognized as a mechanism for limiting the regenerative potential of stem cells and to protect cells from cancer development. The senescence program is realized through autocrine/paracrine pathways based on the activation of a peculiar senescence-associated secretory phenotype (SASP). We show here that conditioned media (CM) of senescent mesenchymal stem cells (MSCs) contain a set of secreted factors that are able to induce a full senescence response in young cells. To delineate a hallmark of stem cells SASP, we have characterized the factors secreted by senescent MSC identifying insulin-like growth factor binding proteins 4 and 7 (IGFBP4 and IGFBP7) as key components needed for triggering senescence in young MSC. The pro-senescent effects of IGFBP4 and IGFBP7 are reversed by single or simultaneous immunodepletion of either proteins from senescent-CM. The blocking of IGFBP4/7 also reduces apoptosis and promotes cell growth, suggesting that they may have a pleiotropic effect on MSC biology. Furthermore, the simultaneous addition of rIGFBP4/7 increased senescence and induced apoptosis in young MSC. Collectively, these results suggest the occurrence of novel-secreted factors regulating MSC cellular senescence of potential importance for regenerative medicine and cancer therapy.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Severino V,Alessio N,Farina A,Sandomenico A,Cipollaro M,Peluso G,Galderisi U,Chambery Adoi
10.1038/cddis.2013.445subject
Has Abstractpub_date
2013-11-07 00:00:00pages
e911issn
2041-4889pii
cddis2013445journal_volume
4pub_type
杂志文章abstract::Psoriasis is an autoimmune skin disease, where chronic immune responses due to exaggerated cytokine signaling, abnormal differentiation, and evasion of keratinocytes apoptosis plays a crucial role in mediating abnormal keratinocytes hyperproliferation. From the therapeutic perspective, the molecules with strong anti-p...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-2212-y
更新日期:2020-01-10 00:00:00
abstract::The DNA-alkylating cytotoxic agent cyclophosphamide (CTX) is commonly used in the clinic to treat hematological malignancies like lymphomas and leukemias as well as solid tumors, but shows dose-dependent potentially life-threatening toxicities and can induce secondary malignancies. Thus, the clinical utility of CTX wo...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.108
更新日期:2017-03-16 00:00:00
abstract::As a deubiqutinase Otub1 stabilizes and promotes the oncogenic activity of the transcription factor c-Maf in multiple myeloma (MM), a malignancy of plasma cells. In the screen for bioactive inhibitors of the Otub1/c-Maf axis for MM treatment, nanchangmycin (Nam), a polyketide antibiotic, was identified to suppress c-M...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03017-4
更新日期:2020-09-30 00:00:00
abstract::The rapid, typically all-or-none process of mitochondrial outer membrane permeabilization (MOMP) constitutes a primary cell death decision that is controlled by the Bcl-2 family interactome. However, how strict all-or-none MOMP decisions are governed by and emanate from the dynamic interplay of pro- and antiapoptotic ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0464-6
更新日期:2018-04-01 00:00:00
abstract::Cancer cells secrete abundant exosomes, and the secretion can be promoted by an increase of intracellular Ca2+. Stromal interaction molecule 1 (STIM1) plays a key role in shaping Ca2+ signals. MicroRNAs (miRNAs) have been reported to be potential therapeutic targets for many diseases, including breast cancer. Recently...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03304-0
更新日期:2021-01-04 00:00:00
abstract::HMG20A (also known as iBRAF) is a chromatin factor involved in neuronal differentiation and maturation. Recently small nucleotide polymorphisms (SNPs) in the HMG20A gene have been linked to type 2 diabetes mellitus (T2DM) yet neither expression nor function of this T2DM candidate gene in islets is known. Herein we dem...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0272-z
更新日期:2018-02-15 00:00:00
abstract::Serum deprivation or withdrawal induces apoptosis in endothelial cells, resulting in endothelial cell dysfunction that is associated with cardiovascular disease. However, there is still limited information on the role of miRNA in serum deprivation-induced apoptosis. Here we found that serum deprivation increased caspa...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.219
更新日期:2017-05-18 00:00:00
abstract::Advanced glycation end products (AGEs) can stimulate osteoblast apoptosis and have a critical role in the pathophysiology of diabetic osteoporosis. Mitochondrial abnormalities are closely related to osteoblast dysfunction. However, it remains unclear whether mitochondrial abnormalities are involved in AGE-induced oste...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0718-3
更新日期:2018-06-04 00:00:00
abstract::Transplantation of neural progenitors derived from human embryonic stem cells (hESCs) provides a potential therapy for ischemic stroke. However, poor graft survival within the host environment has hampered the benefits and applications of cell-based therapies. The present investigation tested a preconditioning strateg...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2009.22
更新日期:2010-01-01 00:00:00
abstract::Cell death plays a pivotal role in animal development and tissue homeostasis. Dysregulation of this process is associated with a wide variety of human diseases, including developmental and immunological disorders, neurodegenerative diseases and tumors. While the fundamental role of JNK pathway in cell death has been e...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-2135-7
更新日期:2019-11-26 00:00:00
abstract::The ubiquitin E3 ligase DELTEX1 (DTX1) is specifically downregulated in gastric cancer tissues, and expression of DTX1 is linked to better prognoses and survival in gastric cancer. Cellular FLICE inhibitory protein (c-FLIP) is known for its pivotal role in the resistance of cancer cells to death receptor-induced cell ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0165-6
更新日期:2018-01-26 00:00:00
abstract::The biological function of E26 transformation-specific (ETS) transcription factor EHF/ESE-3 in human cancers remains largely unknown, particularly gastric cancer. The aim of this study was to explore the role of EHF in tumorigenesis and its potential as a therapeutic target in gastric cancer. By using quantitative RT-...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.346
更新日期:2016-10-27 00:00:00
abstract::Hepatocyte transplantation as a substitute strategy of orthotopic liver transplantation is being studied for treating end-stage liver diseases. Several technical hurdles must be overcome in order to achieve the therapeutic liver repopulation, such as the problem of insufficient expansion of the transplanted hepatocyte...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.230
更新日期:2014-05-22 00:00:00
abstract::Diffusely infiltrating gliomas are among the most prognostically discouraging neoplasia in human. Temozolomide (TMZ) in combination with radiotherapy is currently used for the treatment of glioblastoma (GBM) patients, but less than half of the patients respond to therapy and chemoresistance develops rapidly. Epigeneti...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.245
更新日期:2014-06-05 00:00:00
abstract::Plant-derived dietary antioxidants have attracted considerable interest in recent past for their chemopreventive and cancer therapeutic abilities in animal models. Thymoquinone (TQ) is the major bioactive constituent of volatile oil of Nigella sativa and has been shown to exert various pharmacological properties, such...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.172
更新日期:2013-06-06 00:00:00
abstract::Malignant gliomas, the most common solid tumors in the central nervous system, are essentially incurable due to their rapid growth and very invasive nature. One potential approach to eradicating glioma cells is to force these cells to undergo terminal differentiation and, in the process, to irreversible postmitotic ar...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.425
更新日期:2014-10-16 00:00:00
abstract::Redox imbalance generates multiple cellular damages leading to oxidative stress-mediated pathological conditions such as neurodegenerative diseases and cancer progression. Therefore, maintenance of reactive oxygen species (ROS) homeostasis is most important that involves well-defined antioxidant machinery. In the pres...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.355
更新日期:2014-08-28 00:00:00
abstract::Ionizing radiation (IR) response has been extensively investigated in BMSCs with an increasing consensus that this type of cells showed relative radiosensitivity in vitro analysis. However, the underlying mechanism of IR-induced injury of BMSCs has not been elucidated. In current study, the regulatory role of miR-22/R...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1373-z
更新日期:2019-03-07 00:00:00
abstract::We explored the activity of SIRT1 activators (SRT501 and SRT2183) alone and in combination with panobinostat in a panel of malignant lymphoid cell lines in terms of biological and gene expression responses. SRT501 and SRT2183 induced growth arrest and apoptosis, concomitant with deacetylation of STAT3 and NF-κB, and r...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.159
更新日期:2013-05-16 00:00:00
abstract::Normal cells require adhesion to extracellular matrix for survival. Cell detachment causes a drastic increase in reactive oxygen species (ROS) that promotes anoikis. In the present study, we observed that upon detachment from matrix, human mammary epithelial cells strongly upregulate manganese superoxide dismutase (Mn...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.20
更新日期:2013-02-21 00:00:00
abstract::Mammalian female fertility is limited by the number and quality of oocytes in the ovarian reserve. The number of oocytes is finite since all germ cells cease proliferation to become oocytes in fetal life. Moreover, 70-80% of the initial oocyte population is eliminated during fetal and neonatal development, restricting...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-2019-x
更新日期:2019-10-17 00:00:00
abstract::Retinal ganglion cells (RGCs) undergo rapid cell death by apoptosis after injury but can be rescued by suppression of caspase-2 (CASP2) using an siRNA to CASP2 (siCASP2). Pigment epithelium-derived factor (PEDF), has neuroprotective and anti-angiogenic functions and protects RGC from death. The purpose of this study w...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1379-6
更新日期:2019-02-04 00:00:00
abstract::The majority of developmentally programmed cell death (PCD) is mediated by caspase-dependent apoptosis; however, additional modalities, including autophagy-dependent cell death, have important spatiotemporally restricted functions. Autophagy involves the engulfment of cytoplasmic components in a double membrane vesicl...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1368-9
更新日期:2019-02-08 00:00:00
abstract::Caveolin-1 (CAV1) is a crucial regulator of lipid accumulation and metabolism. Previous studies have shown that global Cav1 deficiency affects lipid metabolism and hepatic steatosis. We aimed to analyze the consequences of hepatocyte-specific Cav1 knockout under healthy conditions and upon non-alcoholic fatty liver di...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2295-5
更新日期:2020-02-06 00:00:00
abstract::Cholera toxin (CT) is a potent mucosal adjuvant and oral administration of ovalbumin (OVA) antigens plus CT induces OVA-specific CD8+ cytotoxic T lymphocytes (CTLs) and IgA production in intestinal mucosa. However, the mechanisms of induction of these immune responses remain unknown. Intestinal OVA-specific CD8+ CTLs ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0665-z
更新日期:2018-05-24 00:00:00
abstract::Triple-negative breast cancers (TNBCs) are aggressive forms of breast carcinoma associated with a high rate of recidivism. In this paper, we report the production of mammospheres from three lines of TNBC cells and demonstrate that both parthenolide (PN) and its soluble analog dimethylaminoparthenolide (DMAPT) suppress...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.94
更新日期:2016-04-14 00:00:00
abstract::Adaptive responses of skeletal muscle regulate the nuclear shuttling of the sarcomeric protein Ankrd2 that can transduce different stimuli into specific adaptations by interacting with both structural and regulatory proteins. In a genome-wide expression study on Ankrd2-knockout or -overexpressing primary proliferating...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.525
更新日期:2014-01-16 00:00:00
abstract::Psoriasis is characterized by keratinocyte hyperproliferation. While significant progress has been made in understanding the molecular mechanism regulating the proliferation of keratinocytes, little is known about the epigenetic factors that control this process. EZH2 and EZH2 mediated trimethylation of histone H3 lys...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03028-1
更新日期:2020-10-03 00:00:00
abstract::Temozolomide (TMZ) is an alkylating agent currently used as first-line therapy for gliomas treatment due to its DNA-damaging effect. However, drug resistance occurs, preventing multi-cycle use of this chemotherapeutic agent. One of the major mechanisms of cancer drug resistance is enhanced activity of a DNA repair enz...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/cddis.2013.388
更新日期:2013-10-24 00:00:00
abstract::The δ opioid receptor (DOR) is involved in the regulation of malignant transformation and tumor progression of hepatocellular carcinoma (HCC). However, regulation of the DOR in HCC remains poorly defined. We found that miR-874 was identified as a negative regulator of the DOR, which is a direct and functional target o...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0131-3
更新日期:2018-01-26 00:00:00