C/EBPα deficiency in podocytes aggravates podocyte senescence and kidney injury in aging mice.

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 C/EBPα in podocyte senescence and kidney aging by generating a genetically modified mouse model of chronological aging in which C/EBPα was selectively deleted in podocytes and by overexpressing C/EBPα in cultured podocytes, in which premature senescence was induced by treatment with adriamycin. Moreover, we illuminated the mechanisms by which podocyte senescence causes tubular impairment by stimulating HK-2 cells with bovine serum albumin (BSA) and chloroquine. Our findings suggest that C/EBPα knockout in podocytes aggravates podocyte senescence through the AMPK/mTOR pathway, leading to glomerulosclerosis, and that subsequent albuminuria exacerbates the epithelial-mesenchymal transdifferentiation of senescent tubular cells by suppressing autophagy. These observations highlight the importance of C/EBPα as a new potential target in kidney aging.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Zhang L,Zhou F,Yu X,Zhu Y,Zhou Y,Liu J,Liu Y,Ma Q,Zhang Y,Wang W,Chen N

doi

10.1038/s41419-019-1933-2

subject

Has Abstract

pub_date

2019-09-17 00:00:00

pages

684

issue

10

issn

2041-4889

pii

10.1038/s41419-019-1933-2

journal_volume

10

pub_type

杂志文章
  • ΔNp63α-induced DUSP4/GSK3β/SNAI1 pathway in epithelial cells drives endometrial fibrosis.

    abstract::Epithelial homeostasis plays an essential role in maintaining endometrial function. But the epithelial role in endometrial fibrosis has been less studied. Previously, we showed that ectopic expression of ΔNp63α is associated with fibrosis process and epithelial dysfunction in endometria of patients with intrauterine a...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2666-y

    authors: Zhao G,Li R,Cao Y,Song M,Jiang P,Wu Q,Zhou Z,Zhu H,Wang H,Dai C,Liu D,Yao S,Lv H,Wang L,Dai J,Zhou Y,Hu Y

    更新日期:2020-06-11 00:00:00

  • Microglia-derived TNF-α mediates endothelial necroptosis aggravating blood brain-barrier disruption after ischemic stroke.

    abstract::Endothelium (EC) is a key component of blood-brain barrier (BBB), and has an important position in the neurovascular unit. Its dysfunction and death after cerebral ischemic/reperfusion (I/R) injury not only promote evolution of neuroinflammation and brain edema, but also increase the risk of intracerebral hemorrhage o...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1716-9

    authors: Chen AQ,Fang Z,Chen XL,Yang S,Zhou YF,Mao L,Xia YP,Jin HJ,Li YN,You MF,Wang XX,Lei H,He QW,Hu B

    更新日期:2019-06-20 00:00:00

  • Cell density-dependent proteolysis by HtrA1 induces translocation of zyxin to the nucleus and increased cell survival.

    abstract::Proteases modulate critical processes in cutaneous tissue repair to orchestrate inflammation, cell proliferation and tissue remodeling. However, the functional consequences and implications in healing impairments of most cleavage events are not understood. Using iTRAQ-based Terminal Amine Isotopic Labeling of Substrat...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-02883-2

    authors: Sabino F,Madzharova E,Auf dem Keller U

    更新日期:2020-08-21 00:00:00

  • Cycloheximide promotes paraptosis induced by inhibition of cyclophilins in glioblastoma multiforme.

    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

    authors: Wang L,Gundelach JH,Bram RJ

    更新日期:2017-05-18 00:00:00

  • Hepatocyte caveolin-1 modulates metabolic gene profiles and functions in non-alcoholic fatty liver disease.

    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

    authors: Han M,Piorońska W,Wang S,Nwosu ZC,Sticht C,Wang S,Gao Y,Ebert MP,Dooley S,Meyer C

    更新日期:2020-02-06 00:00:00

  • TCF3, a novel positive regulator of osteogenesis, plays a crucial role in miR-17 modulating the diverse effect of canonical Wnt signaling in different microenvironments.

    abstract::Wnt signaling pathways are a highly conserved pathway, which plays an important role from the embryonic development to bone formation. The effect of Wnt pathway on osteogenesis relies on their cellular environment and the expression of target genes. However, the molecular mechanism of that remains unclear. On the basi...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.65

    authors: Liu W,Liu Y,Guo T,Hu C,Luo H,Zhang L,Shi S,Cai T,Ding Y,Jin Y

    更新日期:2013-03-14 00:00:00

  • Polymerase independent repression of FoxO1 transcription by sequence-specific PARP1 binding to FoxO1 promoter.

    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

    authors: Tian YN,Chen HD,Tian CQ,Wang YQ,Miao ZH

    更新日期:2020-01-28 00:00:00

  • Menin mediates epigenetic regulation via histone H3 lysine 9 methylation.

    abstract::Menin, encoded by the multiple endocrine neoplasia type 1 (MEN1) gene, is a tumor suppressor that leads to multiple endocrine tumors upon loss of its function. Menin functions as a transcriptional activator by tethering MLL complex to mediate histone H3 K4 methylation. It also functions as a repressor. However, the mo...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.98

    authors: Yang YJ,Song TY,Park J,Lee J,Lim J,Jang H,Kim YN,Yang JH,Song Y,Choi A,Lee HY,Jo CH,Han JW,Kim ST,Youn HD,Cho EJ

    更新日期:2013-04-11 00:00:00

  • Cell death-based treatment of glioblastoma.

    abstract::Cancer cells including glioblastoma have typically evolved multiple mechanisms to escape programmed cell death in order to maintain their survival. Defects in cell death mechanisms not only facilitate tumorigenesis but also ensure resistance to current anticancer therapies. This emphasizes that targeting cell death pa...

    journal_title:Cell death & disease

    pub_type: 杂志文章,评审

    doi:10.1038/s41419-017-0021-8

    authors: Fulda S

    更新日期:2018-01-25 00:00:00

  • Chloride channels are necessary for full platelet phosphatidylserine exposure and procoagulant activity.

    abstract::Platelets enhance thrombin generation at sites of vascular injury by exposing phosphatidylserine during necrosis-like cell death. Anoctamin 6 (Ano6) is required for Ca(2+)-dependent phosphatidylserine exposure and is defective in patients with Scott syndrome, a rare bleeding disorder. Ano6 may also form Cl(-) channels...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.495

    authors: Harper MT,Poole AW

    更新日期:2013-12-19 00:00:00

  • MicroRNA-302 induces proliferation and inhibits oxidant-induced cell death in human adipose tissue-derived mesenchymal stem cells.

    abstract::Mesenchymal stem cells (MSCs) are a heterogeneous population of cells that proliferate in vitro as plastic-adherent cells, have a fibroblast-like morphology, form colonies in vitro and can differentiate into bone, cartilage and fat cells. The abundance, ease and repeatable access to subcutaneous adipose tissue and the...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.344

    authors: Kim JY,Shin KK,Lee AL,Kim YS,Park HJ,Park YK,Bae YC,Jung JS

    更新日期:2014-08-21 00:00:00

  • Transglutaminase 2 mediates UV-induced skin inflammation by enhancing inflammatory cytokine production.

    abstract::UV irradiation elicits acute inflammation in the skin by increasing proinflammatory cytokine production in keratinocytes. However, the downstream protein target(s) that link UV radiation to the activation of signaling pathways responsible for cytokine expression have not been fully elucidated. In this study, we report...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.550

    authors: Lee SJ,Lee KB,Son YH,Shin J,Lee JH,Kim HJ,Hong AY,Bae HW,Kwon MA,Lee WJ,Kim JH,Lee DH,Jeong EM,Kim IG

    更新日期:2017-10-26 00:00:00

  • Neutrophil extracellular traps promote macrophage pyroptosis in sepsis.

    abstract::In response to infection, polymorphonuclear neutrophils (PMN) are recruited in the infectious sites, and employ three major strategies to fight against the microbes including phagocytosis, degranulation, and neutrophil extracellular traps (NETs). NETs are a meshwork of chromatin fibers mixed with granule-derived antim...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0538-5

    authors: Chen L,Zhao Y,Lai D,Zhang P,Yang Y,Li Y,Fei K,Jiang G,Fan J

    更新日期:2018-05-22 00:00:00

  • Keratin 80 promotes migration and invasion of colorectal carcinoma by interacting with PRKDC via activating the AKT pathway.

    abstract::Little is known about the function of Keratin 80 (KRT80), an epithelial keratin, in cancer. This study investigated the role of KRT80 in the prognosis of colorectal carcinoma (CRC) and the underlying mechanisms involved in CRC migration and invasion. We analyzed the expression of KRT80 using The Cancer Genome Atlas an...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-1030-y

    authors: Li C,Liu X,Liu Y,Liu X,Wang R,Liao J,Wu S,Fan J,Peng Z,Li B,Wang Z

    更新日期:2018-09-27 00:00:00

  • Non-viral FoxM1 gene delivery to hepatocytes enhances liver repopulation.

    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

    authors: Xiang D,Liu CC,Wang MJ,Li JX,Chen F,Yao H,Yu B,Lu L,Borjigin U,Chen YX,Zhong L,Wangensteen KJ,He ZY,Wang X,Hu YP

    更新日期:2014-05-22 00:00:00

  • The roles of long noncoding RNAs in breast cancer metastasis.

    abstract::Breast cancer is the most significant threat to female health. Breast cancer metastasis is the major cause of mortality in breast cancer patients. To fully unravel the molecular mechanisms that underlie the breast cancer cell metastasis is critical for developing strategies to improve survival and prognosis in breast ...

    journal_title:Cell death & disease

    pub_type: 杂志文章,评审

    doi:10.1038/s41419-020-02954-4

    authors: Liu L,Zhang Y,Lu J

    更新日期:2020-09-14 00:00:00

  • MBNL1 reverses the proliferation defect of skeletal muscle satellite cells in myotonic dystrophy type 1 by inhibiting autophagy via the mTOR pathway.

    abstract::Skeletal muscle atrophy is one of the clinical symptoms of myotonic dystrophy type 1 (DM1). A decline in skeletal muscle regeneration is an important contributor to muscle atrophy. Skeletal muscle satellite cells (SSCs) drive skeletal muscle regeneration. Increased autophagy can reduce the proliferative capacity of SS...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-02756-8

    authors: Song KY,Guo XM,Wang HQ,Zhang L,Huang SY,Huo YC,Zhang G,Feng JZ,Zhang RR,Ma Y,Hu QZ,Qin XY

    更新日期:2020-07-18 00:00:00

  • The p75 receptor mediates axon growth inhibition through an association with PIR-B.

    abstract::The Nogo receptor and paired immunoglobulin-like receptor B (PIR-B) are receptors for three myelin-derived axon-growth inhibitors, including myelin-associated glycoprotein (MAG). In this study, we report that the p75 receptor is required for the signal transduction of PIR-B, which interacted with p75 upon ligand bindi...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2011.85

    authors: Fujita Y,Takashima R,Endo S,Takai T,Yamashita T

    更新日期:2011-09-01 00:00:00

  • Molecular analysis of axonal-intrinsic and glial-associated co-regulation of axon degeneration.

    abstract::Wallerian degeneration is an active program tightly associated with axonal degeneration, required for axonal regeneration and functional recovery after nerve damage. Here we provide a functional molecular foundation for our undertstanding of the complex non-cell autonomous role of glial cells in the regulation of axon...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.489

    authors: Catenaccio A,Llavero Hurtado M,Diaz P,Lamont DJ,Wishart TM,Court FA

    更新日期:2017-11-09 00:00:00

  • Drp1 regulates mitochondrial dysfunction and dysregulated metabolism in ischemic injury via Clec16a-, BAX-, and GSH- pathways.

    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

    authors: Duan C,Kuang L,Xiang X,Zhang J,Zhu Y,Wu Y,Yan Q,Liu L,Li T

    更新日期:2020-04-20 00:00:00

  • High-fat diet feeding and palmitic acid increase CRC growth in β2AR-dependent manner.

    abstract::Epidemiology studies indicate that consumption of high-fat diet (HFD) is directly associated with the development of colorectal cancer (CRC). However, the exact component in HFD and the mechanism underlying its effect on CRC growth remained unclear. Our study shows that HFD feeding increases β2AR expression in the xen...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1958-6

    authors: Fatima S,Hu X,Huang C,Zhang W,Cai J,Huang M,Gong RH,Chen M,Ho AHM,Su T,Wong HLX,Bian Z,Kwan HY

    更新日期:2019-09-26 00:00:00

  • SIRT1 suppresses the migration and invasion of gastric cancer by regulating ARHGAP5 expression.

    abstract::Gastric cancer (GC) ranks among the top five malignant tumors worldwide by the incidence and mortality rate. However, the mechanisms underlying its progression are poorly understood. In this study, we investigated the role of SIRT1, a class III deacetylase, in the invasion and metastasis of GC. Here, we found that kno...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-1033-8

    authors: Dong G,Wang B,An Y,Li J,Wang X,Jia J,Yang Q

    更新日期:2018-09-24 00:00:00

  • The JAK2/STAT3 and mitochondrial pathways are essential for quercetin nanoliposome-induced C6 glioma cell death.

    abstract::The formulation of quercetin nanoliposomes (QUE-NLs) has been shown to enhance QUE antitumor activity in C6 glioma cells. At high concentrations, QUE-NLs induce necrotic cell death. In this study, we probed the molecular mechanisms of QUE-NL-induced C6 glioma cell death and examined whether QUE-NL-induced programmed c...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.242

    authors: Wang G,Wang JJ,Chen XL,Du SM,Li DS,Pei ZJ,Lan H,Wu LB

    更新日期:2013-08-01 00:00:00

  • Circulating microRNAs in breast cancer: novel diagnostic and prognostic biomarkers.

    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

    authors: Hamam R,Hamam D,Alsaleh KA,Kassem M,Zaher W,Alfayez M,Aldahmash A,Alajez NM

    更新日期:2017-09-07 00:00:00

  • Cracking the code of neuronal apoptosis and survival.

    abstract::Neuronal apoptosis and survival are tightly controlled processes that regulate cell fate during the development of the central nervous system and its homeostasis throughout adulthood. A new study in primary cultures of cerebellar granule neurons identified common transcriptional cascades during rescue from apoptosis b...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2015.309

    authors: Cavallaro S

    更新日期:2015-11-05 00:00:00

  • Release and activity of histone in diseases.

    abstract::Histones and their post-translational modifications have key roles in chromatin remodeling and gene transcription. Besides intranuclear functions, histones act as damage-associated molecular pattern molecules when they are released into the extracellular space. Administration of exogenous histones to animals leads to ...

    journal_title:Cell death & disease

    pub_type: 杂志文章,评审

    doi:10.1038/cddis.2014.337

    authors: Chen R,Kang R,Fan XG,Tang D

    更新日期:2014-08-14 00:00:00

  • E2F1 mediated DDX11 transcriptional activation promotes hepatocellular carcinoma progression through PI3K/AKT/mTOR pathway.

    abstract::The DEAD/DEAH box helicase 11 (DDX11) plays vital roles in regulating the initiation of DNA replication. However, its precise function and regulation in hepatocellular carcinoma (HCC) have never been reported yet. In the current study, we found that DDX11 was overexpressed in HCC tissues. High DDX11 expression was pos...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2478-0

    authors: Yu Y,Zhao D,Li K,Cai Y,Xu P,Li R,Li J,Chen X,Chen P,Cui G

    更新日期:2020-04-24 00:00:00

  • Deficiency in the autophagy modulator Dram1 exacerbates pyroptotic cell death of Mycobacteria-infected macrophages.

    abstract::DNA damage regulated autophagy modulator 1 (DRAM1) is a stress-inducible regulator of autophagy and cell death. DRAM1 has been implicated in cancer, myocardial infarction, and infectious diseases, but the molecular and cellular functions of this transmembrane protein remain poorly understood. Previously, we have propo...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2477-1

    authors: Zhang R,Varela M,Forn-Cuní G,Torraca V,van der Vaart M,Meijer AH

    更新日期:2020-04-24 00:00:00

  • P53-induced miR-1249 inhibits tumor growth, metastasis, and angiogenesis by targeting VEGFA and HMGA2.

    abstract::MicroRNAs (miRNAs) are important class of functional regulators involved in human cancers development, including colorectal cancer (CRC). Exploring aberrantly expressed miRNAs may provide us with new insights into the initiation and development of CRC by functioning as oncogenes or tumor suppressors. The aim of our st...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-1188-3

    authors: Chen X,Zeng K,Xu M,Liu X,Hu X,Xu T,He B,Pan Y,Sun H,Wang S

    更新日期:2019-02-12 00:00:00

  • MiR-142-3p is downregulated in aggressive p53 mutant mouse models of pancreatic ductal adenocarcinoma by hypermethylation of its locus.

    abstract::Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive disease with poor prognostic implications. This is partly due to a large proportion of PDACs carrying mutations in TP53, which impart gain-of-function characteristics that promote metastasis. There is evidence that microRNAs (miRNAs) may play a role in...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0628-4

    authors: Godfrey JD,Morton JP,Wilczynska A,Sansom OJ,Bushell MD

    更新日期:2018-05-29 00:00:00