Abstract:
:Chronic hyperglycemia causes a progressive decrease of β-cell function and mass in type 2 diabetic patients. Growing evidence suggests that augment of autophagy may be an effective approach to protect β cells against various extra-/intracellular stimuli. In this study, we thus investigated whether bone marrow-derived mesenchymal stem cells (BM-MSCs) could ameliorate chronic high glucose (HG)-induced β-cell injury through modulation of autophagy. Prolonged exposure to HG decreased cell viability, increased cell apoptosis and impaired basal insulin secretion and glucose-stimulated insulin secretion of INS-1 cells, but BM-MSC treatment significantly alleviated these glucotoxic alternations. In addition, western blotting displayed upregulated expression of Beclin1 and LC3-II in INS-1 cells co-cultured with BM-MSCs. Results from immunofluorescence staining and transmission electronic microscope analysis also revealed that BM-MSCs promoted autophagosomes and autolysosomes formation in HG-treated INS-1 cells. However, it should be noted that inhibition of autophagy significantly diminished the protective effects of BM-MSCs on HG-treated INS-1 cells, suggesting that the improvement of β-cell function and survival induced by BM-MSCs was mediated through autophagy. Furthermore, our results showed that BM-MSCs improved mitochondrial function and reduced reactive oxygen species production in HG-treated INS-1 cells, largely owing to autophagic clearance of impaired mitochondria. In vivo study was performed in rats with type 2 diabetes (T2D). BM-MSC infusion not only ameliorated hyperglycemia, but also promoted restoration of pancreatic β cells in T2D rats. Meanwhile, BM-MSC infusion upregulated LAMP2 expression and enhanced formation of autophagosomes and autolysosomes, combined with reduced β-cell apoptosis and increased number of insulin granules. These findings together indicated that BM-MSCs could protect β cells against chronic HG-induced injury through modulation of autophagy in vitro and in vivo. This study unveiled novel evidence of BM-MSCs as an ideal strategy to enhance autophagy for treatment of T2D mellitus.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Zhao K,Hao H,Liu J,Tong C,Cheng Y,Xie Z,Zang L,Mu Y,Han Wdoi
10.1038/cddis.2015.230subject
Has Abstractpub_date
2015-09-17 00:00:00pages
e1885issn
2041-4889pii
cddis2015230journal_volume
6pub_type
杂志文章abstract::The sex-determining region Y (SRY)-box (SOX) family has a crucial role in carcinogenesis and cancer progression. However, the role of SOX12 and the mechanism by which it is dysregulated in colorectal cancer (CRC) remain unclear. Here we analyzed SOX12 expression patterns in two independent CRC cohorts (cohort I, n = 3...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1481-9
更新日期:2019-03-11 00:00:00
abstract::P300/CBP-associated factor (PCAF), a histone acetyltransferase (HAT), has been found to regulate numerous cell signaling pathways controlling cell fate by acetylating both histone and non-histone proteins. We previously reported that PCAF upregulates cell apoptosis by inactivating Serine/Threonine Protein Kinase 1 (AK...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.76
更新日期:2015-04-09 00:00:00
abstract::The voltage-gated K+ channel has key roles in the vasculature and in atrial excitability and contributes to apoptosis in various tissues. In this study, we have explored its regulation by carbon monoxide (CO), a product of the cytoprotective heme oxygenase enzymes, and a recognized toxin. CO inhibited recombinant Kv1....
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.568
更新日期:2017-11-02 00:00:00
abstract::B-cell lymphoma-2 (Bcl-2) proteins mediate intrinsic-, or mitochondrial-, initiated apoptosis. We have investigated the structure and function of the least characterized Bcl-2 family member, Bcl-B, solving the crystal structure of a Bcl-B:Bim complex to 1.9 Å resolution. Bcl-B is distinguished from other Bcl-2 family ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2012.178
更新日期:2012-12-13 00:00:00
abstract::B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax) is a member of the Bcl-2 protein family having a pivotal role in triggering cell commitment to apoptosis. Bax is latent and monomeric in the cytosol but transforms into its lethal, mitochondria-embedded oligomeric form in response to cell stress, leading to the rele...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.210
更新日期:2013-06-20 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::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::Glial cell line-derived neurotrophic factor (GDNF) has strong neuroprotective and neurorestorative effects on dopaminergic (DA) neurons in the substantia nigra (SN); however, the underlying molecular mechanisms remain to be fully elucidated. In this study, we found that the expression level of transcription factor Six...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.120
更新日期:2016-05-05 00:00:00
abstract::Noncoding RNAs plays an important role in hepatocellular carcinoma (HCC). Here, we show that miR-124 was downregulated in HCC tissues and that the ectopic expression of miR-124 inhibited the proliferation and migration of HCC cells. We proposed that aquaporin 3 (AQP3) is a direct target of miR-124. AQP3 was upregulate...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0204-3
更新日期:2018-02-07 00:00:00
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journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.90
更新日期:2013-04-04 00:00:00
abstract::Homeodomain-interacting protein kinase 2 (HIPK2) is a multitalented coregulator of an increasing number of transcription factors and cofactors involved in cell death and proliferation in several organs and systems. As Hipk2(-/-) mice show behavioral abnormalities consistent with cerebellar dysfunction, we investigated...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.298
更新日期:2015-12-03 00:00:00
abstract::Growing evidence indicates that cell adhesion to extracellular matrix (ECM) plays an important role in cancer chemoresistance. Leukemic T cells express several adhesion receptors of the β1 integrin subfamily with which they interact with ECM. However, the role of β1 integrins in chemoresistance of T-cell acute lymphob...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1593-2
更新日期:2019-05-01 00:00:00
abstract::Breast cancer is the leading cause of cancer-related death in women worldwide. Human epidermal growth factor receptor 2 (HER2)-positive subtype comprises 20% of sporadic breast cancers and is an aggressive disease. While targeted therapies have greatly improved its management, primary and acquired resistance remain a ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-021-03414-3
更新日期:2021-01-26 00:00:00
abstract::Drug resistance is a major problem in cancer therapy. A growing body of evidence demonstrates that the tumor microenvironment, including cancer-associated fibroblasts (CAFs), can modulate drug sensitivity in tumor cells. We examined the effect of primary human CAFs on p53 induction and cell viability in prostate cance...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.225
更新日期:2017-06-01 00:00:00
abstract::Gallbladder cancer (GBC) is one of the most common malignancy of the biliary tract characterized by its high chemoresistant tendency. Although great progresses have been made in recent decades for treating many cancers with anticancer drugs, effective therapeutics methods for anti-GBC are still lacking. Therefore, inv...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.178
更新日期:2017-05-11 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::ZAK, a mixed lineage kinase, is often described as a positive or negative regulator of cell growth. We identified it as one of the top hits in our kinome cDNA screen for potent regulators of epithelial mesenchymal transition (EMT). Ectopic expression of ZAK promoted EMT phenotypes and apoptosis resistance in multiple ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0161-x
更新日期:2018-02-02 00:00:00
abstract::Effective management of breast cancer depends on early diagnosis and proper monitoring of patients' response to therapy. However, these goals are difficult to achieve because of the lack of sensitive and specific biomarkers for early detection and for disease monitoring. Accumulating evidence in the past several years...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/cddis.2017.440
更新日期:2017-09-07 00:00:00
abstract::Although targeting of the death receptors (DRs) DR4 and DR5 still appears a suitable antitumoral strategy, the limited clinical responses to recombinant soluble TNF-related apoptosis inducing ligand (TRAIL) necessitate novel reagents with improved apoptotic activity/tumor selectivity. Apoptosis induction by a single-c...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2012.29
更新日期:2012-04-12 00:00:00
abstract::The emergence of drug resistant tumours that are able to escape cell death pose a major problem in the treatment of cancers. Tumours develop resistance to DNA-damaging chemotherapeutic agents by acquiring the ability to repair their DNA. Combination therapies that induce DNA damage and disrupt the DNA damage repair pr...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.365
更新日期:2013-10-10 00:00:00
abstract::Recent studies identified a highly tumorigenic subpopulation of glioma stem cells (GSCs) within malignant gliomas. GSCs are proposed to originate from transformed neural stem cells (NSCs). Several pathways active in NSCs, including the Notch pathway, were shown to promote proliferation and tumorigenesis in GSCs. Notch...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2012.65
更新日期:2012-06-21 00:00:00
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journal_title:Cell death & disease
pub_type: 已发布勘误
doi:10.1038/s41419-018-0639-1
更新日期:2018-05-24 00:00:00
abstract::Proton pump inhibitors (PPI) target tumour acidic pH and have an antineoplastic effect in melanoma. The PPI esomeprazole (ESOM) kills melanoma cells through a caspase-dependent pathway involving cytosolic acidification and alkalinization of tumour pH. In this paper, we further investigated the mechanisms of ESOM-induc...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2010.67
更新日期:2010-10-21 00:00:00
abstract::In most clinical trials, human mesenchymal stem cells (hMSCs) are expanded in vitro before implantation. The genetic stability of human stem cells is critical for their clinical use. However, the relationship between stem-cell expansion and genetic stability is poorly understood. Here, we demonstrate that within the n...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.211
更新日期:2013-06-27 00:00:00
abstract::HIV-1 Nef protein has key roles at almost all stages of the viral life cycle. We assessed the role of the Nef/eEF1A (eukaryotic translation elongation factor 1-alpha) complex in nucleocytoplasmic shuttling in primary human macrophages. Nuclear retention experiments and inhibition of the exportin-t (Exp-t) pathway sugg...
journal_title:Cell death & disease
pub_type: 杂志文章,收录出版
doi:10.1038/cddis.2012.32
更新日期:2012-04-05 00:00:00
abstract::Chronic psychological stress has been demonstrated to play an important role in several severe diseases, but whether it affects disease therapy or not remains unclear. Mesenchymal stem cells (MSCs) have been demonstrated to have therapeutic potentials in treating tissue injury based on their multidifferentiation poten...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.257
更新日期:2014-06-26 00:00:00
abstract::Autophagy (macroautophagy) is an evolutionarily conserved lysosomal degradation process, in which a cell degrades long-lived proteins and damaged organelles. Recently, accumulating evidence has revealed the core molecular machinery of autophagy in carcinogenesis; however, the intricate relationship between autophagy a...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/cddis.2013.422
更新日期:2013-10-31 00:00:00
abstract::Cancer is the second leading cause of death worldwide. Current treatment strategies based on multi-agent chemotherapy and/or radiation regimens have improved overall survival in some cases. However, resistance to apoptosis often develops in cancer cells, and its occurrence is thought to contribute to treatment failure...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.217
更新日期:2017-05-18 00:00:00
abstract::Poly(ADP-ribose) polymerase 1 (PARP1) regulates gene transcription in addition to functioning as a DNA repair factor. Forkhead box O1 (FoxO1) is a transcription factor involved in extensive biological processes. Here, we report that PARP1 binds to two separate motifs on the FoxO1 promoter and represses its transcripti...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2265-y
更新日期:2020-01-28 00:00:00
abstract::The anti-apoptotic protein MCL-1 is a key regulator of cancer cell survival and a known resistance factor for small-molecule BCL-2 family inhibitors such as ABT-263 (navitoclax), making it an attractive therapeutic target. However, directly inhibiting this target requires the disruption of high-affinity protein-protei...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.561
更新日期:2015-01-15 00:00:00