Abstract:
:Podocyte apoptosis is a major mechanism that leads to proteinuria in many chronic kidney diseases. However, the concert mechanisms that cause podocyte apoptosis in these kidney diseases are not fully understood. The Rho family of small GTPases has been shown to be required in maintaining podocyte structure and function. Recent studies have indicated that podocyte-specific deletion of Cdc42 in vivo, but not of RhoA or Rac1, leads to congenital nephrotic syndrome and glomerulosclerosis. However, the underlying cellular events in podocyte controlled by Cdc42 remain unclear. Here, we assessed the cellular mechanisms by which Cdc42 regulates podocyte apoptosis. We found that the expression of Cdc42 and its activity were significantly decreased in high glucose-, lipopolysaccharide- or adriamycin-injured podocytes. Reduced Cdc42 expression in vitro and in vivo by small interfering RNA and selective Cdc42 inhibitor ML-141, respectively, caused podocyte apoptosis and proteinuria. Our results further demonstrated that insufficient Cdc42 or Nwasp, its downstream effector, could decrease the mRNA and protein expression of YAP, which had been regarded as an anti-apoptosis protein in podocyte. Moreover, our data indicated that the loss of stress fibers caused by Cdc42/Nwasp deficiency also decreased Yes-associated protein (YAP) mRNA and protein expression, and induced podocyte apoptosis. Podocyte apoptosis induced by Cdc42/Nwasp/stress fiber deficiency was significantly inhibited by overexpressing-active YAP. Thus, the Cdc42/Nwasp/stress fibers/YAP signal pathway may potentially play an important role in regulating podocyte apoptosis. Maintaining necessary Cdc42 would be one potent way to prevent proteinuria kidney diseases.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Huang Z,Zhang L,Chen Y,Zhang H,Zhang Q,Li R,Ma J,Li Z,Yu C,Lai Y,Lin T,Zhao X,Zhang B,Ye Z,Liu S,Wang W,Liang X,Liao R,Shi Wdoi
10.1038/cddis.2016.51subject
Has Abstractpub_date
2016-03-17 00:00:00pages
e2142issn
2041-4889pii
cddis201651journal_volume
7pub_type
杂志文章abstract::The PDF and HTML versions of the article have been updated to include the Creative Commons Attribution 4.0 International License information. ...
journal_title:Cell death & disease
pub_type: 已发布勘误
doi:10.1038/s41419-018-0834-0
更新日期:2018-07-16 00:00:00
abstract::The adaptation of mitochondrial homeostasis to ischemic injury is not fully understood. Here, we studied the role of dynamin-related protein 1 (Drp1) in this process. We found that mitochondrial morphology was altered in the early stage of ischemic injury while mitochondrial dysfunction occurred in the late stage of i...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2461-9
更新日期:2020-04-20 00:00:00
abstract::Thioredoxin-interacting protein (TXNIP) is involved in oxidative stress and apoptosis in diabetic retinopathy. However, the role of TXNIP in the removal of damaged mitochondria (MT) via mitophagy, a process of macroautophagy, remains unexplored. Here we investigate the associated cellular and molecular mechanisms unde...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.190
更新日期:2017-05-11 00:00:00
abstract::WD repeat protein 79 (WDR79) is a member of the WD-repeat protein family and functions as a scaffold protein during telomerase assembly, Cajal body formation and DNA double strand break repair. We have previously shown that WDR79 is frequently overexpressed in cell lines and tissues derived from non-small cell lung ca...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.162
更新日期:2017-04-13 00:00:00
abstract::Spermatogenesis associated serine rich 2 (SPATS2) has been reported to contribute to the tumorigenesis of multiple malignancies. The molecular function of SPATS2 in hepatocellular carcinoma (HCC) is still not fully understood. In this study, we aimed to investigate the expression pattern and function roles of SPATS2 i...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03039-y
更新日期:2020-10-09 00:00:00
abstract::Accumulating evidence suggested the participation of long noncoding RNAs (lncRNAs) in regulating various biological processes so as to affecting cancer progression. However, the functional role of most lncRNAs in colorectal carcer (CRC) is still largely covered. In the present study, we disclosed SNHG14 as a carcinoge...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1707-x
更新日期:2019-07-04 00:00:00
abstract::Providing a conducive microenvironment is critical to increase survival of transplanted stem cells in regenerative therapy. Hyperglycemia promotes stem cell death impairing cardiac regeneration in the diabetic heart. Understanding the molecular mechanisms of high glucose-induced stem cell death is important for improv...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2367-6
更新日期:2020-03-13 00:00:00
abstract::Patients with high-grade serous ovarian cancer (HGSC) frequently receive platinum-based chemotherapeutics, such as cisplatin. Cisplatin binds to DNA and induces DNA-damage culminating in mitochondria-mediated apoptosis. Interestingly, mitochondrial DNA is critically affected by cisplatin but its relevance in cell deat...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-2081-4
更新日期:2019-11-07 00:00:00
abstract::Despite successful antiretroviral drug therapy, a subset of human immunodeficiency virus-1 (HIV)-positive individuals still display synaptodendritic simplifications and functional cognitive impairments referred to as HIV-associated neurocognitive disorders (HANDs). The neurological damage observed in HAND subjects can...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1920-7
更新日期:2019-09-12 00:00:00
abstract::The Pierre Robin Sequence (PRS), consisting of cleft palate, glossoptosis and micrognathia, is a common human birth defect. However, how this abnormality occurs remains largely unknown. Here we report that neural crest cell (NCC)-specific knockout of transferrin receptor (Tfrc), a well known transferrin transporter pr...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.170
更新日期:2016-06-30 00:00:00
abstract::Interleukin-17 receptor B (IL-17RB), a member of the IL-17 receptor family activated by IL-17B/IL-17E, has been shown to be involved in inflammatory diseases. However, the regulation and function of IL-17RB in Helicobacter pylori (H. pylori) infection, especially in the early-phase is still unknown. Here, we found tha...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1312-z
更新日期:2019-01-28 00:00:00
abstract::Liver cancer is the second most common cause of cancer-related death worldwide. Approximately 70-90% of primary liver cancers are hepatocellular carcinoma (HCC). Currently, HCC patient prognosis is unsatisfactory due to high metastasis and/or post-surgical recurrence rates. Therefore, new therapeutic methods for inhib...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0534-9
更新日期:2018-05-01 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::Glioblastoma multiform (GBM) is the most common brain tumor characterized by a dismal prognosis. GBM cancer stem cells (gCSC) or tumor-initiating cells are the cell population within the tumor-driving therapy resistance and recurrence. While temozolomide (TMZ), an alkylating agent, constitutes the first-line chemother...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1477-5
更新日期:2019-03-13 00:00:00
abstract::Quantitative and kinetic analyses of apoptotic cell death are integral components of exploring cell biology, measuring cellular stress responses, and performing high-throughput genomic/RNAi/drug screens. Here, we present a detailed method that integrates robust kinetic real-time high-content imaging with Annexin V lab...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.332
更新日期:2016-12-01 00:00:00
abstract::Interleukin 7 receptor (il7r), a transmembrane receptor, belongs to the type I cytokine receptor family. Il7r is involved in the pathogenesis of neurodegenerative disorders, such as multiple sclerosis. Targeted knockdown of il7r leads to delayed myelination, highlighting the potential role of il7r in the development o...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0337-z
更新日期:2018-02-15 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::Many recent studies have uncovered the necessary role for the receptor-interacting protein kinase 1 (RIP1) in regulating apoptosis and necrosis that cells undergo in response to various cellular stresses. However, the functional significance of RIP1 in promoting cancer cells survival remains poorly understood. Here, w...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0714-7
更新日期:2018-06-07 00:00:00
abstract::The high mortality in breast cancer is often associated with metastatic progression in patients. Previously we have demonstrated that testes-specific protease 50 (TSP50), an oncogene overexpressed in breast cancer samples, could promote cell proliferation and tumorigenesis. However, whether TSP50 also has a key role i...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.61
更新日期:2015-03-26 00:00:00
abstract::Glucocorticoids (GCs) represent an important component of modern treatment regimens for fludarabine-refractory or TP53-defective chronic lymphocytic leukemia (CLL). However, GC therapy is not effective in all patients. The molecular mechanisms responsible for GC-induced apoptosis and resistance were therefore investig...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2012.102
更新日期:2012-08-16 00:00:00
abstract::Protein tyrosine kinase 7 (PTK7) and cancer-associated fibroblasts (CAFs) play important roles in cancer stemness, respectively. However, little is known about interaction between CAFs and PTK7 in cancers. In this study, we showed that PTK7 was significantly correlated with the Wnt/β-Catenin pathway and aggressive cli...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1116-6
更新日期:2018-10-22 00:00:00
abstract::Protein kinase CK2 is a highly conserved and constitutively active Ser/Thr-kinase that phosphorylates a large number of substrates, resulting in increased cell proliferation and survival. A known target of CK2 is Akt, a player in the PI3K/Akt/mTORC1 signaling pathway, which is aberrantly activated in 32% of colorectal...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1306-x
更新日期:2019-01-25 00:00:00
abstract::4-hydroxyphenylpyruvate dioxygenase (HPD) is an important modifier of tyrosine metabolism. However, the precise contribution of HPD to cancer metabolism and tumorigenesis remains unclear. In this study, we found that HPD was highly expressed in lung cancer and its higher expression correlated with poor prognosis in lu...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1756-1
更新日期:2019-07-08 00:00:00
abstract::Mitochondrial Lon is a multi-function matrix protease with chaperone activity. However, little literature has been undertaken into detailed investigations on how Lon regulates apoptosis through its chaperone activity. Accumulating evidences indicate that various stresses induce transportation of p53 to mitochondria an...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0730-7
更新日期:2018-06-13 00:00:00
abstract::The ubiquitination-proteasome and degradation system is an essential process that regulates protein homeostasis. This system is involved in the regulation of cell proliferation, differentiation and survival, and dysregulations in this system lead to pathologies including cancers. The ubiquitination system is an enzyma...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/cddis.2012.217
更新日期:2013-01-17 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::Despite decades of research, the pathogenesis of acute respiratory distress syndrome (ARDS) remains poorly understood, thus impeding the development of effective treatment. Diffuse alveolar damage (DAD) and lung epithelial cell death are prominent features of ARDS. Lung epithelial cells are the first line of defense a...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.282
更新日期:2015-12-10 00:00:00
abstract::Mitochondrial ferritin (FtMt) is a mitochondrially localized protein possessing ferroxidase activity and the ability to store iron. FtMt overexpression in cultured cells protects against oxidative damage by sequestering redox-active, intracellular iron. Here, we found that acute exhaustive exercise significantly incre...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.372
更新日期:2016-11-17 00:00:00
abstract::Acute promyelocytic leukemia (APL) therapy involves the compounds cytotoxic to both malignant tumor and normal cells. Relapsed APL is resistant to subsequent chemotherapy. Novel agents are in need to kill APL cells selectively with minimal toxicity. DDX5 has been recognized to be a novel target to suppress acute myelo...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-02759-5
更新日期:2020-07-20 00:00:00
abstract::H. pylori infection is one of the leading causes of gastric cancer and the pathogenicity of H. pylori infection is associated with its ability to induce chronic inflammation and apoptosis resistance. While H. pylori infection-induced expression of pro-inflammatory cytokines for chronic inflammation is well studied, th...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-02894-z
更新日期:2020-08-21 00:00:00