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Oihana Iriondo, Yarong Liu, Grace Lee, Mostafa Elhodaky, Christian Jimenez, Lin Li, Julie Lang, Pin Wang, Min Yu
Triple-negative breast cancer (TNBC) is a highly metastatic subtype of breast cancer that has limited therapeutic options. Thus, developing novel treatments for metastatic TNBC is an urgent need. Here, we show that nanoparticle-mediated delivery of transforming growth factor-β1-activated kinase-1 (TAK1) inhibitor 5Z-7-Oxozeaenol can inhibit TNBC lung metastasis in most animals tested. P38 is a central signal downstream of TAK1 in TNBC cells in TAK1-mediated response to multiple cytokines. Following co-culturing with macrophages or fibroblasts, TNBC cells express interleukin-1 (IL1) or tumor necrosis factor-α (TNFα), respectively...
May 18, 2018: Nature Communications
Jun Zhou, Jiying Zhong, Zhenxing Huang, Meijuan Liao, Sen Lin, Jia Chen, Hongtao Chen
Renal fibrosis is a common and characteristic symptom of chronic kidney disease (CKD). However, the molecular mechanisms of renal fibrosis remain elusive. Ischemia injury, as a major cause of AKI, deserves more attention in order to improve the knowledge of AKI-induced fibrosis. Transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) interacts directly with TGF-β, which play a critical role in the progression of fibrosis. Therefore, the present study aimed to investigate the role of TAK1 in the pathogenesis of ischemia-induced renal fibrosis...
April 16, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Huiying Yan, Dingding Zhang, Yongxiang Wei, Hongbin Ni, Weibang Liang, Huasheng Zhang, Shuangying Hao, Wei Jin, Kuanyu Li, Chun-Hua Hang
Accumulating of evidence suggests that activation of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) exacerbates early brain injury (EBI) following subarachnoid hemorrhage (SAH) by provoking pro-inflammatory and pro-apoptotic signaling. Myeloid differentiation primary response protein 88 (MyD88) is an endogenous adaptor protein in the toll-like receptors (TLRs) and interleukin (IL) -1β family signaling pathways and acts as a bottle neck in the NF-κB and MAPK pathways. Here, we used ST2825, a selective inhibitor of MyD88, to clarify whether inhibiting MyD88 could provide neuroprotection in EBI following SAH...
November 17, 2017: Scientific Reports
Lei Li, Bingqing Huang, Shiyang Song, Hareshwaree Sohun, Zhiheng Rao, Luyuan Tao, Qike Jin, Jingjing Zeng, Rongzhou Wu, Kangting Ji, Jiafeng Lin, Lianpin Wu, Maoping Chu
A20, a negative regulator of nuclear factor κB signaling, has been shown to attenuate atherosclerotic events. Transforming growth factor beta-activated kinase 1 (TAK1) plays a critical role in TNFα-induced atherosclerosis via endothelial nitric oxide (NO) synthase (eNOS) uncoupling and NO reduction. In the study, we investigated the hypothesis that A20 protected endothelial cell injury induced by TNFα through modulating eNOS activity and TAK1 signalling. Human umbilical vein endothelial cells (HUVECs) were stimulated by TNFα...
September 12, 2017: Oncotarget
Lei Li, Bingqing Huang, Shiyang Song, Hareshwaree Sohun, Zhiheng Rao, Luyuan Tao, Qike Jin, Jingjing Zeng, Rongzhou Wu, Kangting Ji, Jiafeng Lin, Lianpin Wu, Maoping Chu
A20, a negative regulator of nuclear factor κB signaling, has been shown to attenuate atherosclerotic events. Transforming growth factor beta-activated kinase 1 (TAK1) plays a critical role in TNFα-induced atherosclerosis via endothelial nitric oxide (NO) synthase (eNOS) uncoupling and NO reduction. In the study, we investigated the hypothesis that A20 protected endothelial cell injury induced by TNFα through modulating eNOS activity and TAK1 signalling. Human umbilical vein endothelial cells (HUVECs) were stimulated by TNFα...
May 25, 2017: Oncotarget
Hugo W Huth, Daniel M Santos, Humberto D Gravina, Jarbas M Resende, Alfredo M Goes, Maria Elena de Lima, Catherine Ropert
Tumor cells capture the signaling pathways used by normal tissue to promote their own survival and dissemination and among them, the NF-κB and MAPK pathways (ERK, JNK and p38). MAPK activation has ambiguous effects on tumor cell fate depending on cell type, cancer stage and the engaged MAPK isoforms. A synthetic peptide named LyeTx II, derived from the venom of the Brazilian spider Lycosa erythrognatha, was capable of increasing MDA-MB-231 aggressive breast cancer cell proliferation as indicated by MTT and BrdU (5-bromo-2'-deoxyuridine) incorporation assay and cell migration...
April 2017: Oncology Reports
Lianpin Wu, Zhiyong Cao, Ling Ji, Liqin Mei, Qike Jin, Jingjing Zeng, Jiafeng Lin, Maoping Chu, Lei Li, Xiangjun Yang
We investigated the role of tumour necrosis factor receptor (TNFR)-associated death domain (TRADD) on pressure overload-induced cardiac hypertrophy and the underlying molecular mechanisms by using a TRADD deficiency mice model. 6-8 weeks wild-type and TRADD knockout mice were performed to transverse aorta constriction (TAC) or sham operation (6-8 mice for each group). 14 days after TAC, cardiac function was measured by echocardiography, as well as by pathological and molecular analyses of heart samples. The expressions of cardiac hypertrophic and fibrotic markers were detected by qPCR...
February 5, 2017: Biochemical and Biophysical Research Communications
Lijuan Chen, Jia Huang, Yan-Xiao Ji, Fanghua Mei, Pi-Xiao Wang, Ke-Qiong Deng, Xi Jiang, Genshan Ma, Hongliang Li
Tripartite motif (TRIM) 8 functions as an E3 ubiquitin ligase, interacting with and ubiquitinating diverse substrates, and is implicated in various pathological processes. However, the function of TRIM8 in the heart remains largely uncharacterized. This study aims to explore the role of TRIM8 in the development of pathological cardiac hypertrophy. Mice and isolated neonatal rat cardiomyocytes overexpressing or lacking TRIM8 were examined in several experiments. The effect of aortic banding-induced cardiac hypertrophy was analyzed by echocardiographic, pathological and molecular analyses...
February 2017: Hypertension
Peng Sun, Shun-Zong Song, Shuang Jiang, Xia Li, You-Li Yao, Yan-Ling Wu, Li-Hua Lian, Ji-Xing Nan
The current study was designed to investigate the anti-inflammatory effect of salidroside (SDS) and the underlying mechanism by using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in vitro and a mouse model of binge drinking-induced liver injury in vivo. SDS downregulated protein expression of toll-like receptor 4 (TLR4) and CD14. SDS inhibited LPS-triggered phosphorylation of LPS-activated kinase 1 (TAK1), p38, c-Jun terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). Degradation of IκB-α and nuclear translocation of nuclear factor (NF)-κB were effectively blocked by SDS...
November 9, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Ruiting Liu, Guorong Wang, Chang Liu, Jian Qiu, Likun Yan, Xiaojun Li, Xiaoqiang Wang
DNA-binding protein A (dbpA) has been reported associated with the pathogenesis and development of various cancers. However, no evidence showed the gene expression profiling alternation involved in dbpA knockdown in colorectal cancer (CRC) cells. Small interference RNA (siRNA) method was used to knock down dbpA expression in SW620 cells. The changes of gene expression profiles in dbpA knockdown SW620 cells were determined by microarray analysis and Western blot. A total of 578 genes expressed differentially (twofold change), 181 genes were up-regulated, and 397 down-regulated in the dbpA knockdown group in comparison with the control group...
December 2016: Cell Biology International
Kenichi Mishima, Hiroshi Kitoh, Bisei Ohkawara, Tatsuya Okuno, Mikako Ito, Akio Masuda, Naoki Ishiguro, Kinji Ohno
The transcription factor, runt-related transcription factor 2 (Runx2), plays a pivotal role in the differentiation of the mesenchymal stem cells to the osteochondroblast lineages. We found by the drug repositioning strategy that a proton pump inhibitor, lansoprazole, enhances nuclear accumulation of Runx2 and induces osteoblastogenesis of human mesenchymal stromal cells. Systemic administration of lansoprazole to a rat femoral fracture model increased osteoblastogenesis. Dissection of signaling pathways revealed that lansoprazole activates a noncanonical bone morphogenic protein (BMP)-transforming growth factor-beta (TGF-β) activated kinase-1 (TAK1)-p38 mitogen-activated protein kinase (MAPK) pathway...
December 2015: EBioMedicine
Xiaoyu Liu, Tingting Yang, Langxi Miao, Yan-Ai Mei, Changlong Hu
BACKGROUND/AIMS: Arachidonic acid (AA) and its metabolites are important endogenous lipid messengers. In this study, we test the effect of Leukotriene B4 (LTB4), a 5-lipoxygenase metabolite of AA, on L-type calcium channels in A7r5 rat aortic vascular smooth muscle cells. METHODS: L-type calcium channel currents were recorded by a patch-clamp technique. The mRNA expression of CaV1.2 was determined by Real-time RT-PCR. The protein expression of CaV1.2 and p38 activity was determined by Western blot analysis...
2015: Cellular Physiology and Biochemistry
Jie Zhang, Bing Li, Haixia Wu, Jiayao Ou, Rongbin Wei, Junjun Liu, Wenping Cai, Xiaodong Liu, Shouliang Zhao, Jianhua Yang, Lili Zhou, Shangfeng Liu, Aibin Liang
Treatment failure in cancer chemotherapy is largely due to the toxic effects of chemotherapeutic agents on normal cells/tissues. The proteasome inhibitor bortezomib has been successfully applied to treat multiple myeloma (MM), but there are some common adverse reactions in the clinic including peripheral neuropathy (PN). The TAK1 selective inhibitor 5Z-7-oxozeaenol has been widely studied in cancer therapy. Here, we investigated the potential synergy of bortezomib and 5Z-7-oxozeaenol in Burkitt's lymphoma (BL) cell lines...
January 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Xiaofeng Teng, Na Wei, Hong Chen, Kaihua Zhai
No abstract text is available yet for this article.
October 2015: Journal of Molecular Neuroscience: MN
I-Ting Chen, Pang-Hung Hsu, Wan-Ching Hsu, Nien-Jung Chen, Ping-Hui Tseng
Toll-like receptor 4 (TLR4) plays an important role in innate immunity by eliciting inflammation. Upon receptor engagement, transforming growth factor β-activated kinase 1 (TAK1) is an essential mediator that transmits a signal from the receptor to downstream effectors, IκB kinase (IKK) and the mitogen-activated protein kinases (MAPKs), which control the production of inflammatory cytokines. However, the association between phosphorylation and ubiquitination of TAK1 is not yet clear. Here, we examined the crosstalk between phosphorylation and polyubiquitination of TAK1 and further investigated the mechanism of distinct activation of MAPKs and IKK...
2015: Scientific Reports
Dingding Zhang, Huiying Yan, Hua Li, Shuangying Hao, Zong Zhuang, Ming Liu, Qing Sun, Yiqing Yang, Mengliang Zhou, Kuanyu Li, Chunhua Hang
Accumulating evidence suggests that activation of mitogen-activated protein kinases (MAPKs) and nuclear factor NF-κB exacerbates early brain injury (EBI) following subarachnoid hemorrhage (SAH) by provoking proapoptotic and proinflammatory cellular signaling. Here we evaluate the role of TGFβ-activated kinase 1 (TAK1), a critical regulator of the NF-κB and MAPK pathways, in early brain injury following SAH. Although the expression level of TAK1 did not present significant alternation in the basal temporal lobe after SAH, the expression of phosphorylated TAK1 (Thr-187, p-TAK1) showed a substantial increase 24 h post-SAH...
August 7, 2015: Journal of Biological Chemistry
Mineko Tomomura, Ryuichiro Suzuki, Yoshiaki Shirataki, Hiroshi Sakagami, Nobuaki Tamura, Akito Tomomura
Rhinacanthin C is a naphthoquinone ester with anti-inflammatory activity, found in Rhinacanthus nasutus (L) Kurz (Acanthaceae). We found that rhinacanthin C inhibited osteoclast differentiation stimulated by the receptor activator of nuclear factor-κB ligand (RANKL) in mouse bone marrow macrophage cultures, although the precise molecular mechanisms underlying this phenomenon are unclear. In this study, we investigated the inhibitory mechanisms of rhinacanthin C in osteoclastogenesis. Rhinacanthin C suppressed RANKL-induced nuclear factor of activated T cells c1 (NFATc1) expression...
2015: PloS One
Emily F A van 't Wout, Annemarie van Schadewijk, Ria van Boxtel, Lucy E Dalton, Hanna J Clarke, Jan Tommassen, Stefan J Marciniak, Pieter S Hiemstra
Pseudomonas aeruginosa infection can be disastrous in chronic lung diseases such as cystic fibrosis and chronic obstructive pulmonary disease. Its toxic effects are largely mediated by secreted virulence factors including pyocyanin, elastase and alkaline protease (AprA). Efficient functioning of the endoplasmic reticulum (ER) is crucial for cell survival and appropriate immune responses, while an excess of unfolded proteins within the ER leads to "ER stress" and activation of the "unfolded protein response" (UPR)...
June 2015: PLoS Pathogens
Jingjing Lin, Daekee Lee, Yongwon Choi, Soo Young Lee
The E3 ubiquitin ligase TRAF6 [tumor necrosis factor (TNF) receptor (TNFR)-associated factor 6] and the associated kinase TAK1 [transforming growth factor-β (TGF-β)-activated kinase 1] are key components of the signaling pathways that activate nuclear factor κB (NF-κB) and mitogen-activated protein kinases (MAPKs) in response to various stimuli. The cytokine RANKL (receptor activator of NF-κB ligand) is essential for the differentiation of bone marrow cells into bone-resorbing osteoclasts through the activation of NF-κB and MAPK...
June 2, 2015: Science Signaling
Hui Quan, Joung-Min Kim, Hyun-Jung Lee, Seong-Heon Lee, Jeong-Il Choi, Hong-Beom Bae
Recent studies have suggested that 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) increases macrophage phagocytosis through adenosine monophosphate-activated protein kinase (AMPK). However, little information is available on the effects of AICAR on the clearance of apoptotic cells by macrophages, known as efferocytosis, which is essential in maintaining tissue homeostasis and resolving inflammation. AICAR increased p38 MAPK activation and the phagocytosis of apoptotic cells by macrophages, which were inhibited by the p38 MAPK inhibitor, SB203580, the TGF-beta-activated kinase 1 (TAK1) inhibitor, (5Z)-7-oxozeaenol, and siRNA-mediated knock-down of p38α...
2015: PloS One
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