Abstract:
:We previously showed that injury by partial duct ligation (PDL) in adult mouse pancreas activates Neurogenin 3 (Ngn3)(+) progenitor cells that can differentiate to β cells ex vivo. Here we evaluate the role of Ngn3(+) cells in β cell expansion in situ. PDL not only induced doubling of the β cell volume but also increased the total number of islets. β cells proliferated without extended delay (the so-called 'refractory' period), their proliferation potential was highest in small islets, and 86% of the β cell expansion was attributable to proliferation of pre-existing β cells. At sufficiently high Ngn3 expression level, upto 14% of all β cells and 40% of small islet β cells derived from non-β cells. Moreover, β cell proliferation was blunted by a selective ablation of Ngn3(+) cells but not by conditional knockout of Ngn3 in pre-existing β cells supporting a key role for Ngn3(+) insulin(-) cells in β cell proliferation and expansion. We conclude that Ngn3(+) cell-dependent proliferation of pre-existing and newly-formed β cells as well as reprogramming of non-β cells contribute to in vivo β cell expansion in the injured pancreas of adult mice.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Van de Casteele M,Leuckx G,Baeyens L,Cai Y,Yuchi Y,Coppens V,De Groef S,Eriksson M,Svensson C,Ahlgren U,Ahnfelt-Rønne J,Madsen OD,Waisman A,Dor Y,Jensen JN,Heimberg Hdoi
10.1038/cddis.2013.52subject
Has Abstractpub_date
2013-03-07 00:00:00pages
e523issn
2041-4889pii
cddis201352journal_volume
4pub_type
杂志文章abstract::Anaplastic Thyroid Cancer (ATC) is an aggressive malignancy with limited therapeutic options and dismal patient survival. We have previously shown MADD to be differentially overexpressed in multiple cancer histologies and to contribute to tumor cell growth and survival. Therefore, we targeted MADD by gene silencing, e...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1351-5
更新日期:2019-02-13 00:00:00
abstract::This is the first study to investigate the hepatoprotective effect of CQ on acute liver injury caused by carbon tetrachloride (CCl4) in a murine model and the underlying molecular mechanisms. Ninety-six mice were randomly divided into the control (n = 8), CQ (n = 8), CCl4 (n = 40), and CCl4 + CQ (n = 40) treatment gro...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1136-2
更新日期:2018-11-26 00:00:00
abstract::Hepatocellular carcinoma (HCC) is the major type of primary liver cancer. Genomic studies have revealed that HCC is a heterogeneous disease with multiple subtypes. BRG1, encoded by the SMARCA4 gene, is a key component of SWI/SNF chromatin-remodeling complexes. Based on TCGA studies, somatic mutations of SMARCA4 occur ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2289-3
更新日期:2020-02-04 00:00:00
abstract::Kidney aging leads to an increased incidence of end-stage renal disease (ESRD) in the elderly, and aging is a complex biological process controlled by signaling pathways and transcription factors. Podocyte senescence plays a central role in injury resulting from kidney aging. Here, we demonstrated the critical role of...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1933-2
更新日期:2019-09-17 00:00:00
abstract::Unloading-induced bone loss is a threat to human health and can eventually result in osteoporotic fractures. Although the underlying molecular mechanism of unloading-induced bone loss has been broadly elucidated, the pathophysiological role of long noncoding RNAs (lncRNAs) in this process is unknown. Here, we identifi...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2574-1
更新日期:2020-05-19 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Cell death & disease
pub_type: 已发布勘误
doi:10.1038/s41419-019-2189-6
更新日期:2020-01-06 00:00:00
abstract::Previously, we confirmed that sphingosine kinase 1 (SphK1) inhibition improves sepsis-associated liver injury. High-mobility group box 1 (HMGB1) translocation participates in the development of acute liver failure. However, little information is available on the association between SphK1 and HMGB1 translocation during...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03255-6
更新日期:2020-12-06 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::Recent evidence indicates that long noncoding RNAs (lncRNAs) have a critical role in the regulation of cellular processes such as differentiation, proliferation, and metastasis. These lncRNAs are dysregulated in a variety of cancers and many function as tumor suppressors; however, the regulatory factors involved in si...
journal_title:Cell death & disease
pub_type: 临床试验,杂志文章
doi:10.1038/cddis.2014.256
更新日期:2014-06-26 00:00:00
abstract::The intestinal epithelial monolayer, at the boundary between microbes and the host immune system, plays an important role in the development of inflammatory bowel disease (IBD), particularly as a target and producer of pro-inflammatory TNF. Chronic overexpression of TNF leads to IBD-like pathology over time, but the m...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1275-5
更新日期:2019-02-06 00:00:00
abstract::Increasing evidence indicates that dysregulation of microRNAs (miRNAs) plays a crucial role in human malignancies. Here, we showed that microRNA-422a (miR-422a) expression was dramatically downregulated in gastric cancer (GC) samples and cell lines compared with normal controls, and that its expression level was inver...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0564-3
更新日期:2018-05-01 00:00:00
abstract::Extracorporeal photochemotherapy (ECP) is employed for the management of cutaneous T cell lymphoma (CTCL). ECP involves the extracorporeal exposure of white blood cells (WBCs) to a photosensitizer, 8-methoxypsoralen (8-MOP), in the context of ultraviolet A (UVA) radiation, followed by WBC reinfusion. Historically, the...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1819-3
更新日期:2019-08-02 00:00:00
abstract::Heme oxygenase-1 (HO-1), an inducible enzyme up-regulated in Alzheimer's disease, catabolises heme to biliverdin, Fe2+ and carbon monoxide (CO). CO can protect neurones from oxidative stress-induced apoptosis by inhibiting Kv2.1 channels, which mediates cellular K+ efflux as an early step in the apoptotic cascade. Sin...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.529
更新日期:2014-12-11 00:00:00
abstract::The enteric pathogen enterohemorrhagic Escherichia coli (EHEC) is responsible for outbreaks of bloody diarrhea and hemolytic uremic syndrome (HUS) worldwide. Several molecular mechanisms have been described for the pathogenicity of EHEC; however, the role of bacterial metabolism in the virulence of EHEC during infecti...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0423-2
更新日期:2018-03-07 00:00:00
abstract::As a key member of the forkhead box transcription factors, forkhead box F2 (FOXF2) serves as a transcriptional regulator and regulates downstream gene expression in embryonic development, metabolism and in some common diseases, such as stroke and gastroparesis. Recent studies have shown that aberrant expression of FOX...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/s41419-020-2604-z
更新日期:2020-06-05 00:00:00
abstract::Type 2 diabetes is a chronic metabolic disorder, where failure to maintain normal glucose homoeostasis is associated with, and exacerbated by, obesity and the concomitant-elevated free fatty acid concentrations typically found in these patients. Hyperglycaemia and hyperlipidaemia together contribute to a decline in in...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.203
更新日期:2016-08-11 00:00:00
abstract::Granzyme B (GZMB) is a proapoptotic serine protease that is released by cytotoxic lymphocytes. However, GZMB can also be produced by other cell types and is capable of cleaving extracellular matrix (ECM) proteins. GZMB contributes to abdominal aortic aneurysm (AAA) through an extracellular, perforin-independent mechan...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2011.88
更新日期:2011-09-08 00:00:00
abstract::Glycogen synthase kinase-3β (GSK-3β) has emerged as a critical factor in several pathways involved in hippocampal neuronal maintenance and function. In Huntington's disease (HD), there are early hippocampal deficits both in patients and transgenic mouse models, which prompted us to investigate whether disease-specific...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.104
更新日期:2016-04-28 00:00:00
abstract::Current preclinical models in tumor biology are limited in their ability to recapitulate relevant (patho-) physiological processes, including autophagy. Three-dimensional (3D) growth cultures have frequently been proposed to overcome the lack of correlation between two-dimensional (2D) monolayer cell cultures and huma...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.398
更新日期:2017-08-24 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::Mitochondrial membrane potential provides a valuable indicator of cells' health and functional status. Cytometry- and microscopy-based analyses, in combination with fluorescent probes, are widely used to study mitochondrial behavior related to cellular pathways, most notably - apoptosis. The cyanine dye JC-1 (5,5',6,6...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2012.171
更新日期:2012-11-22 00:00:00
abstract::Nicotinamide N-methyltransferase (NNMT, E.C. 2.1.1.1) N-methylates nicotinamide to produce 1-methylnicotinamide (MeN). We have previously shown that NNMT expression protected against neurotoxin-mediated cell death by increasing Complex I (CxI) activity, resulting in increased ATP synthesis. This was mediated via prote...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.200
更新日期:2013-06-13 00:00:00
abstract::The development of nephrotoxicity largely limits the clinical use of chemotherapy. MiRNAs are able to target various genes and involved in the regulation of diverse cellular processes, including cell apoptosis and death. Our study showed that miR-181a expression was significantly increased after 5-fluorouracil (5-FU) ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0677-8
更新日期:2018-05-23 00:00:00
abstract::p63 is a p53 family transcription factor, which besides unique roles in epithelial development, shares tumor suppressive activity with its homolog p53. The p63 gene has different transcriptional start sites, which generate two N-terminal isoforms (transactivation domain (TA)p63 and amino terminal truncated protein(ΔN)...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.175
更新日期:2013-05-23 00:00:00
abstract::The skin is a high turnover organ, and its constant renewal depends on the rapid proliferation of its progenitor cells. The energy requirement for these metabolically active cells is met by mitochondrial respiration, an ATP generating process driven by a series of protein complexes collectively known as the electron t...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/s41419-020-2649-z
更新日期:2020-06-09 00:00:00
abstract::Given the dense stroma and poor vascularization, access to nutrients is limited in the microenvironment of pancreatic ductal adenocarcinoma (PDA). PDA cells can efficiently recycle various metabolic substrates through the activation of different rescuing pathways, including the autophagy pathway. However, the precise ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1244-z
更新日期:2018-12-11 00:00:00
abstract::Withanolide E, a steroidal lactone from Physalis peruviana, was found to be highly active for sensitizing renal carcinoma cells and a number of other human cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. Withanolide E, the most potent and least toxic of five TRAIL-se...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.38
更新日期:2015-02-26 00:00:00
abstract::Cockayne syndrome (CS) is a progressive developmental and neurodegenerative disorder resulting in premature death at childhood and cells derived from CS patients display DNA repair and transcriptional defects. CS is caused by mutations in csa and csb genes, and patients with csb mutation are more prevalent. A hallmark...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.228
更新日期:2014-05-29 00:00:00
abstract::α-synuclein (α-syn) accumulation and aggregation is a common pathological factor found in synucleinopathies, a group of neurodegenerative disorders that includes Parkinson´s disease (PD). It has been proposed that lipid dyshomeostasis is responsible for the occurrence of PD-related processes, however, the precise role...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03254-7
更新日期:2021-01-07 00:00:00
abstract::Although increasing evidence indicated that deregulation of microRNAs (miRNAs) contributed to tumor initiation and progression, but little is known about the biological role of miR-340 in ovarian cancer (OC). In this study, we found that miR-340 expression was downregulated in OC tissues compared with its expression i...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1604-3
更新日期:2019-05-08 00:00:00