A novel STAT3 inhibitor attenuates angiotensin II-induced abdominal aortic aneurysm progression in mice through modulating vascular inflammation and autophagy.

Abstract:

:Abdominal Aortic aneurysm (AAA) is associated with chronic inflammation, cells apoptosis, and impairment of autophagy. BP-1-102, a novel potent STAT3 inhibitor, has been recently reported to significantly block inflammation-related signaling pathways of JAK2/STAT3 and NF-κB, as well as regulate autophagy. However, its role in vascular inflammation and AAA progression remains to be elucidated. In the present study, the effect and potential mechanisms of BP-1-102 on angiotensin II (AngII) induced AAA in ApoE-/- mice were investigated. AAA was induced in ApoE-/- mice with infusion of AngII for 28 days. BP-1-102 was administrated orally to mice every other day. Mice were sacrificed on day 7, day 14, and day 28 to evaluate the treatment effects. BP-1-102 markedly decreased AAA incidence and aortic diameter, maintained elastin structure and volume, reduced the expression of pro-inflammatory cytokines and MMPs, and inhibited inflammatory cells infiltration. Moreover, BP-1-102 dramatically reduced the expression of JAK2, p-STAT3, p-NF-κB, and Bcl-xL but maintained the expression of LC3B and Beclin in AAA tissues. In vitro, vascular smooth muscle cells (VSMCs) were treated with AngII and/or BP-1-102 at indicated time and concentration. BP-1-102 inhibited AngII-induced JAK2/STAT3 and NF-κB signaling activation and maintained autophagy-related proteins expression in VSMCs. Taken together, our findings suggest that BP-1-102 inhibits vascular inflammation and AAA progression through decreasing JAK2/STAT3 and NF-κB activation and maintaining autophagy.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Wu QY,Cheng Z,Zhou YZ,Zhao Y,Li JM,Zhou XM,Peng HL,Zhang GS,Liao XB,Fu XM

doi

10.1038/s41419-020-2326-2

subject

Has Abstract

pub_date

2020-02-18 00:00:00

pages

131

issue

2

issn

2041-4889

pii

10.1038/s41419-020-2326-2

journal_volume

11

pub_type

杂志文章
  • socs7, a target gene of microRNA-145, regulates interferon-β induction through STAT3 nuclear translocation in bladder cancer cells.

    abstract::We recently reported that microRNA (miR)-145 is downregulated and induces apoptosis in human bladder cancer cells. Also, it is suggested that the ectopic expression of miR-145 induces apoptosis with the induction of TRAIL expression in several cancer cells. Here, we demonstrated a novel mechanism of apoptosis inductio...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.11

    authors: Noguchi S,Yamada N,Kumazaki M,Yasui Y,Iwasaki J,Naito S,Akao Y

    更新日期:2013-02-07 00:00:00

  • Cytotoxicity of apigenin on leukemia cell lines: implications for prevention and therapy.

    abstract::Natural-food-based compounds show substantial promise for prevention and biotherapy of cancers including leukemia. In general, their mechanism of action remains unclear, hampering rational use of these compounds. Herein we show that the common dietary flavonoid apigenin has anticancer activity, but also may decrease c...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2009.18

    authors: Ruela-de-Sousa RR,Fuhler GM,Blom N,Ferreira CV,Aoyama H,Peppelenbosch MP

    更新日期:2010-01-01 00:00:00

  • cBid, Bax and Bcl-xL exhibit opposite membrane remodeling activities.

    abstract::The proteins of the Bcl-2 family have a crucial role in mitochondrial outer membrane permeabilization during apoptosis and in the regulation of mitochondrial dynamics. Current models consider that Bax forms toroidal pores at mitochondria that are responsible for the release of cytochrome c, whereas Bcl-xL inhibits por...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.34

    authors: Bleicken S,Hofhaus G,Ugarte-Uribe B,Schröder R,García-Sáez AJ

    更新日期:2016-02-25 00:00:00

  • Plumbagin inhibits the proliferation and survival of esophageal cancer cells by blocking STAT3-PLK1-AKT signaling.

    abstract::Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers, and it requires novel treatment approaches and effective drugs. In the present study, we found that treatment with plumbagin, a natural compound, reduced proliferation and survival of the KYSE150 and KYSE450 ESCC cell lines in a dose-dependent ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-017-0068-6

    authors: Cao YY,Yu J,Liu TT,Yang KX,Yang LY,Chen Q,Shi F,Hao JJ,Cai Y,Wang MR,Lu WH,Zhang Y

    更新日期:2018-01-16 00:00:00

  • miR-218-5p restores sensitivity to gemcitabine through PRKCE/MDR1 axis in gallbladder cancer.

    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

    authors: Wang H,Zhan M,Xu SW,Chen W,Long MM,Shi YH,Liu Q,Mohan M,Wang J

    更新日期:2017-05-11 00:00:00

  • A role for intracellular zinc in glioma alteration of neuronal chloride equilibrium.

    abstract::Glioma patients commonly suffer from epileptic seizures. However, the mechanisms of glioma-associated epilepsy are far to be completely understood. Using glioma-neurons co-cultures, we found that tumor cells are able to deeply influence neuronal chloride homeostasis, by depolarizing the reversal potential of γ-aminobu...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.437

    authors: Di Angelantonio S,Murana E,Cocco S,Scala F,Bertollini C,Molinari MG,Lauro C,Bregestovski P,Limatola C,Ragozzino D

    更新日期:2014-10-30 00:00:00

  • The lncRNA TUG1 modulates proliferation in trophoblast cells via epigenetic suppression of RND3.

    abstract::Due to limited treatment options, pre-eclampsia (PE) is associated with fetal perinatal and maternal morbidity and mortality. During the causes of PE, failure of uterine spiral artery remodeling which might be related to functioning abnormally of trophoblast cells, result in the occurrence and progression of PE. Recen...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.503

    authors: Xu Y,Ge Z,Zhang E,Zuo Q,Huang S,Yang N,Wu D,Zhang Y,Chen Y,Xu H,Huang H,Jiang Z,Sun L

    更新日期:2017-10-12 00:00:00

  • Circ_0002770, acting as a competitive endogenous RNA, promotes proliferation and invasion by targeting miR-331-3p in melanoma.

    abstract::Melanoma is a kind of tumor that originates from melanocytes and is characterized by chemoresistance and distant metastasis. Although the complete pathogenesis of melanoma remains unclear, increasing evidence suggests that circular RNAs (circRNAs) may be involved. In the present study, we identified a circular RNA, ci...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2444-x

    authors: Qian P,Linbo L,Xiaomei Z,Hui P

    更新日期:2020-04-23 00:00:00

  • Tryptophan-kynurenine pathway attenuates β-catenin-dependent pro-parasitic role of STING-TICAM2-IRF3-IDO1 signalosome in Toxoplasma gondii infection.

    abstract::Recent studies have documented the diverse role of host immunity in infection by the protozoan parasite, Toxoplasma gondii. However, the contribution of the β-catenin pathway in this process has not been explored. Here, we show that AKT-mediated phosphorylated β-catenin supports T. gondii multiplication which is arres...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1420-9

    authors: Majumdar T,Sharma S,Kumar M,Hussain MA,Chauhan N,Kalia I,Sahu AK,Rana VS,Bharti R,Haldar AK,Singh AP,Mazumder S

    更新日期:2019-02-15 00:00:00

  • SOX12 promotes colorectal cancer cell proliferation and metastasis by regulating asparagine synthesis.

    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

    authors: Du F,Chen J,Liu H,Cai Y,Cao T,Han W,Yi X,Qian M,Tian D,Nie Y,Wu K,Fan D,Xia L

    更新日期:2019-03-11 00:00:00

  • Differential activity of GSK-3 isoforms regulates NF-κB and TRAIL- or TNFα induced apoptosis in pancreatic cancer cells.

    abstract::While TRAIL is a promising anticancer agent due to its ability to selectively induce apoptosis in neoplastic cells, many tumors, including pancreatic ductal adenocarcinoma (PDA), display intrinsic resistance, highlighting the need for TRAIL-sensitizing agents. Here we report that TRAIL-induced apoptosis in PDA cell li...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.102

    authors: Zhang JS,Herreros-Villanueva M,Koenig A,Deng Z,de Narvajas AA,Gomez TS,Meng X,Bujanda L,Ellenrieder V,Li XK,Kaufmann SH,Billadeau DD

    更新日期:2014-03-27 00:00:00

  • Metabolism addiction in pancreatic cancer.

    abstract::Pancreatic ductal adenocarcinoma, an aggressively invasive, treatment-resistant malignancy and the fourth leading cause of cancer deaths in the United States, is usually detectable only when already inevitably fatal. Despite advances in genetic screening, mapping and molecular characterization, its pathology remains l...

    journal_title:Cell death & disease

    pub_type: 杂志文章,评审

    doi:10.1038/cddis.2014.38

    authors: Blum R,Kloog Y

    更新日期:2014-02-20 00:00:00

  • Increased plasma levels of CK-18 as potential cell death biomarker in patients with HELLP syndrome.

    abstract::HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome represents a life-threatening pregnancy disorder with high fetal and maternal mortality, but its underlying molecular mechanisms remain unknown. Although apoptosis has been implicated in HELLP syndrome, its pathogenic role remains largely unclear. In th...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.408

    authors: John K,Wielgosz S,Schulze-Osthoff K,Bantel H,Hass R

    更新日期:2013-10-24 00:00:00

  • PIM1 mediates epithelial-mesenchymal transition by targeting Smads and c-Myc in the nucleus and potentiates clear-cell renal-cell carcinoma oncogenesis.

    abstract::Emerging evidence has shown that the PIM serine/threonine kinase family, including PIM1, PIM2 and PIM3, is associated with tumour progression towards metastasis. PIM1, an attractive molecular target, has been identified as a potential prognostic biomarker for haematological and epithelial malignancies. However, to dat...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0348-9

    authors: Zhao B,Liu L,Mao J,Zhang Z,Wang Q,Li Q

    更新日期:2018-02-22 00:00:00

  • Parthenolide and DMAPT exert cytotoxic effects on breast cancer stem-like cells by inducing oxidative stress, mitochondrial dysfunction and necrosis.

    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

    authors: Carlisi D,Buttitta G,Di Fiore R,Scerri C,Drago-Ferrante R,Vento R,Tesoriere G

    更新日期:2016-04-14 00:00:00

  • Calcineurin suppresses AMPK-dependent cytoprotective autophagy in cardiomyocytes under oxidative stress.

    abstract::Calcineurin signalling plays a critical role in the pathogenesis of many cardiovascular diseases. Calcineurin has been proven to affect a series of signalling pathways and to exert a proapoptotic effect in cardiomyocytes. However, whether it is able to regulate autophagy remains largely unknown. Here, we report that p...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.533

    authors: He H,Liu X,Lv L,Liang H,Leng B,Zhao D,Zhang Y,Du Z,Chen X,Li S,Lu Y,Shan H

    更新日期:2014-01-16 00:00:00

  • PIM kinases mediate resistance of glioblastoma cells to TRAIL by a p62/SQSTM1-dependent mechanism.

    abstract::Glioblastoma (GBM) is the most common and aggressive brain tumor and is associated with poor prognosis. GBM cells are frequently resistant to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and finding new combinatorial therapies to sensitize glioma cells to TRAIL remains an important challenge. PIM ki...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-1293-3

    authors: Serrano-Saenz S,Palacios C,Delgado-Bellido D,López-Jiménez L,Garcia-Diaz A,Soto-Serrano Y,Casal JI,Bartolomé RA,Fernández-Luna JL,López-Rivas A,Oliver FJ

    更新日期:2019-01-18 00:00:00

  • Author Correction: Autophagic degradation of caveolin-1 promotes liver sinusoidal endothelial cells defenestration.

    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/s41419-019-1722-y

    authors: Luo X,Wang D,Zhu X,Wang G,You Y,Ning Z,Li Y,Jin S,Huang Y,Hu Y,Chen T,Meng Y,Li X

    更新日期:2019-06-17 00:00:00

  • Inhibition of autophagy increased AGE/ROS-mediated apoptosis in mesangial cells.

    abstract::The aim of our study was to investigate the role of autophagy, a homeostatic process involved in the lysosomal degradation of damaged cell organelles and proteins, in regulating the survival of mesangial cells treated with advanced glycation end products (AGEs). In the present study, AGEs induced mitochondrial depolar...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.322

    authors: Xu L,Fan Q,Wang X,Zhao X,Wang L

    更新日期:2016-11-03 00:00:00

  • 6-Phosphofructo-2-kinase (PFKFB3) promotes cell cycle progression and suppresses apoptosis via Cdk1-mediated phosphorylation of p27.

    abstract::The control of glucose metabolism and the cell cycle must be coordinated in order to guarantee sufficient ATP and anabolic substrates at distinct phases of the cell cycle. The family of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFKFB1-4) are well established regulators of glucose metabolism via their synt...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.292

    authors: Yalcin A,Clem BF,Imbert-Fernandez Y,Ozcan SC,Peker S,O'Neal J,Klarer AC,Clem AL,Telang S,Chesney J

    更新日期:2014-07-17 00:00:00

  • PAX6, modified by SUMOylation, plays a protective role in corneal endothelial injury.

    abstract::Treating corneal endothelial diseases tends to be challenging as human corneal endothelial cells (CECs) do not proliferate in vivo. The pathogenesis or mechanisms underlying injured CECs need further studies. The abnormal expression of PAX6, which is an essential transcription factor for corneal homeostasis, exhibits ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-02848-5

    authors: Yu F,Zhang W,Yan C,Yan D,Zhou M,Chen J,Zhao X,Zhu A,Zhou J,Liu H,Sun H,Fu Y

    更新日期:2020-08-12 00:00:00

  • Transcription factor Six2 mediates the protection of GDNF on 6-OHDA lesioned dopaminergic neurons by regulating Smurf1 expression.

    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

    authors: Gao J,Kang XY,Sun S,Li L,Zhang BL,Li YQ,Gao DS

    更新日期:2016-05-05 00:00:00

  • CD10-/ALDH- cells are the sole cisplatin-resistant component of a novel ovarian cancer stem cell hierarchy.

    abstract::It is long established that tumour-initiating cancer stem cells (CSCs) possess chemoresistant properties. However, little is known of the mechanisms involved, particularly with respect to the organisation of CSCs as stem-progenitor-differentiated cell hierarchies. Here we aimed to elucidate the relationship between CS...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.379

    authors: Ffrench B,Gasch C,Hokamp K,Spillane C,Blackshields G,Mahgoub TM,Bates M,Kehoe L,Mooney A,Doyle R,Doyle B,O'Donnell D,Gleeson N,Hennessy BT,Stordal B,O'Riain C,Lambkin H,O'Toole S,O'Leary JJ,Gallagher MF

    更新日期:2017-10-19 00:00:00

  • Crosstalk between Dpp and Tor signaling coordinates autophagy-dependent midgut degradation.

    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

    authors: Denton D,Xu T,Dayan S,Nicolson S,Kumar S

    更新日期:2019-02-08 00:00:00

  • CARMA2sh and ULK2 control pathogen-associated molecular patterns recognition in human keratinocytes: psoriasis-linked CARMA2sh mutants escape ULK2 censorship.

    abstract::The molecular complexes formed by specific members of the family of CARMA proteins, the CARD domain-containing adapter molecule BCL10 and MALT1 (CBM complex) represent a central hub in regulating activation of the pleiotropic transcription factor NF-κB. Recently, missense mutations in CARMA2sh have been shown to cause...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.51

    authors: Scudiero I,Mazzone P,D'Andrea LE,Ferravante A,Zotti T,Telesio G,De Rubis G,Reale C,Pizzulo M,Muralitharan S,Vito P,Stilo R

    更新日期:2017-02-23 00:00:00

  • Anti-inflammatory effects of a Chinese herbal medicine in atherosclerosis via estrogen receptor β mediating nitric oxide production and NF-κB suppression in endothelial cells.

    abstract::Bu-Shen-Ning-Xin Decoction (BSNXD) administration has alleviated the early pathologic damage of atherosclerosis by inhibiting the adhesion molecule expression and upregulating the estrogen receptor (ER) β expression in endothelial cells, and increasing the serum nitric oxide (NO) level without any effect on serum lipi...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.66

    authors: Wang L,Qiu XM,Hao Q,Li DJ

    更新日期:2013-03-21 00:00:00

  • Discovery of a small-molecule protein kinase Cδ-selective activator with promising application in colon cancer therapy.

    abstract::Protein kinase C (PKC) isozymes play major roles in human diseases, including cancer. Yet, the poor understanding of isozymes-specific functions and the limited availability of selective pharmacological modulators of PKC isozymes have limited the clinical translation of PKC-targeting agents. Here, we report the first ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-017-0154-9

    authors: Bessa C,Soares J,Raimundo L,Loureiro JB,Gomes C,Reis F,Soares ML,Santos D,Dureja C,Chaudhuri SR,Lopez-Haber C,Kazanietz MG,Gonçalves J,Simões MF,Rijo P,Saraiva L

    更新日期:2018-01-18 00:00:00

  • Age-severity matched cytokine profiling reveals specific signatures in Covid-19 patients.

    abstract::A global effort is currently undertaken to restrain the COVID-19 pandemic. Host immunity has come out as a determinant for COVID-19 clinical outcomes, and several studies investigated the immune profiling of SARS-CoV-2 infected people to properly direct the clinical management of the disease. Thus, lymphopenia, T-cell...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-03151-z

    authors: Angioni R,Sánchez-Rodríguez R,Munari F,Bertoldi N,Arcidiacono D,Cavinato S,Marturano D,Zaramella A,Realdon S,Cattelan A,Viola A,Molon B

    更新日期:2020-11-06 00:00:00

  • RREB1-induced upregulation of the lncRNA AGAP2-AS1 regulates the proliferation and migration of pancreatic cancer partly through suppressing ANKRD1 and ANGPTL4.

    abstract::Long noncoding RNAs (lncRNAs) have been reported to be involved in a variety of human diseases, including cancers. However, their mechanisms have not yet been fully elucidated. We investigated lncRNA changes that may be associated with pancreatic cancer (PC) by analyzing published microarray data, and identified AGAP2...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1384-9

    authors: Hui B,Ji H,Xu Y,Wang J,Ma Z,Zhang C,Wang K,Zhou Y

    更新日期:2019-02-27 00:00:00

  • CHD1L contributes to cisplatin resistance by upregulating the ABCB1-NF-κB axis in human non-small-cell lung cancer.

    abstract::Chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) is a recently identified gene associated with malignant tumor progression and patient chemotherapy resistance in human hepatocellular carcinoma (HCC). Previously, we found an association between CHD1L overexpression and poor patient survival in non-s...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1371-1

    authors: Li Y,He LR,Gao Y,Zhou NN,Liu Y,Zhou XK,Liu JF,Guan XY,Ma NF,Xie D

    更新日期:2019-02-04 00:00:00