Hai Li, Baotian Kan, Lingli Song, Yufa Liu, Xiangdong Jian
OBJECTIVE: To elucidate the molecular mechanisms by which safflower yellow (SY) mediates therapeutic effects in rats with paraquat intoxication-induced pulmonary fibrosis. METHODS: Rats received combinations of paraquat, SY, and SB431542, a transforming growth factor (TGF)-β1 receptor antagonist. Survival over 28 days was assessed by Kaplan-Meier analysis. Rat tissue and serum samples were assessed by hematoxylin and eosin staining, Masson's Trichrome staining, immunoblotting, quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and transmission electron microscopy...
September 2020: Journal of International Medical Research
Haipeng Guo, Yao Wei Lu, Zhiqiang Lin, Zhan-Peng Huang, Jianming Liu, Yi Wang, Hee Young Seok, Xiaoyun Hu, Qing Ma, Kathryn Li, Jan Kyselovic, Qingchuan Wang, Jenny L-C Lin, Jim J-C Lin, Douglas B Cowan, Francisco Naya, Yuguo Chen, William T Pu, Da-Zhi Wang
Intercalated discs (ICD), specific cell-to-cell contacts that connect adjacent cardiomyocytes, ensure mechanical and electrochemical coupling during contraction of the heart. Mutations in genes encoding ICD components are linked to cardiovascular diseases. Here, we show that loss of Xinβ, a newly-identified component of ICDs, results in cardiomyocyte proliferation defects and cardiomyopathy. We uncovered a role for Xinβ in signaling via the Hippo-YAP pathway by recruiting NF2 to the ICD to modulate cardiac function...
September 16, 2020: Nature Communications
Di Wang, Lin Lin, Ke Lei, Jiaqi Zeng, Jialiang Luo, Yue Yin, Yao Li, Liyun Zhang, Xiaoli Nie, Daming Zuo, Ledong Sun
BACKGROUND: Wound healing is a complex physiological process that is crucial for reestablishing the epithelial barrier following injury. OBJECTIVE: The aim of this study was to demonstrate the efficacy of calcipotriol, a synthetic vitamin D3 analogue, in wound healing in an acute mice wound model. METHODS: An excision wound model was established in mice, and the wound healing activity of calcipotriol was evaluated. Human keratinocyte cell lines, HaCaT and NHEK, were utilized in in vitro skin wound healing model...
September 7, 2020: Journal of Dermatological Science
Hani Harb, Emmanuel Stephen-Victor, Elena Crestani, Mehdi Benamar, Amir Massoud, Ye Cui, Louis-Marie Charbonnier, Sena Arbag, Safa Baris, Amparito Cunnigham, Juan Manuel Leyva-Castillo, Raif S Geha, Amirhosein J Mousavi, Boris Guennewig, Klaus Schmitz-Abe, Constantinos Sioutas, Wanda Phipatanakul, Talal A Chatila
Elucidating the mechanisms that sustain asthmatic inflammation is critical for precision therapies. We found that interleukin-6- and STAT3 transcription factor-dependent upregulation of Notch4 receptor on lung tissue regulatory T (Treg ) cells is necessary for allergens and particulate matter pollutants to promote airway inflammation. Notch4 subverted Treg cells into the type 2 and type 17 helper (TH 2 and TH 17) effector T cells by Wnt and Hippo pathway-dependent mechanisms. Wnt activation induced growth and differentiation factor 15 expression in Treg cells, which activated group 2 innate lymphoid cells to provide a feed-forward mechanism for aggravated inflammation...
September 14, 2020: Nature Immunology
Eun Hee Ahn, Seong Su Kang, Qi Qi, Xia Liu, Keqiang Ye
The Hippo (MST1/2) pathway plays a critical role in restricting tissue growth in adults and modulating cell proliferation, differentiation, and migration in developing organs. Netrin1, a secreted laminin-related protein, is essential for nervous system development. However, the mechanisms underlying MST1 regulation by the extrinsic signals remain unclear. Here, we demonstrate that Netrin1 reduction in Parkinson's disease (PD) activates MST1, which selectively binds and phosphorylates netrin receptor UNC5B on T428 residue, promoting its apoptotic activation and dopaminergic neuronal loss...
September 14, 2020: Proceedings of the National Academy of Sciences of the United States of America
Christophe Royer, Karolis Leonavicius, Annemarie Kip, Deborah Fortin, Kirtirupa Nandi, Anna Vincent, Celine Jones, Tim Child, Kevin Coward, Chris Graham, Shankar Srinivas
Precise patterning within the 3-dimensional context of tissues, organs and embryos implies that cells can sense their relative position. During preimplantation development, outside and inside cells rely on apicobasal polarity and the Hippo pathway to choose their fate. Despite recent findings suggesting that mechanosensing may be central to this process, the relationship between blastomere geometry (i.e. shape and position) and the Hippo pathway effector YAP remains unknown. We used a highly quantitative approach to analyse information on the geometry and YAP localisation of individual blastomeres of mouse and human embryos...
September 14, 2020: Development
Zhengming Wu, Kun-Liang Guan
Hippo pathway components are structurally and functionally conserved and are notable for their role in controlling organ size. More diverse functions of the Hippo pathway have been recognized, including development, tissue homeostasis, wound healing and regeneration, immunity, and tumorigenesis. During embryogenesis, different signaling pathways are repeatedly and cooperatively activated, leading to differential gene expression in specific developmental contexts. In this article, we present an overview on the regulation and function of the Hippo pathway in mammalian early development...
September 11, 2020: Trends in Biochemical Sciences
Yang Liu, Hao Chen, Jianheng Hao, Zhencheng Li, Tiezheng Hou, Huiqin Hao
In order to investigate the altered expression of microRNAs (miRNAs) in the development of autoimmune hepatitis (AIH), the aberrantly expressed miRNAs in the concanavalin A (Con A)-induced AIH mouse model were identified for the first time with microarray in this study. A total of 49 miRNAs (31 up- and 18 down-regulated) were screened out, and the qRT-PCR validation results of 12 chosen miRNAs were consistent with the microarray data. Combined with the profiling of differently expressed mRNAs in the same model (data not shown), 959 predicted target genes (601 for up- and 358 for down-regulated miRNAs) were obtained according to the intersection of databases miRWalk and miRDB, and several hub genes were obtained from the regulatory networks, including Cadm1 and Mier3 ...
2020: International Journal of Medical Sciences
Kailiang Qiao, Yantao Liu, Zheng Xu, Haohao Zhang, Heng Zhang, Chao Zhang, Zhi Chang, Xinyan Lu, Zhongwei Li, Ce Luo, Yanrong Liu, Cheng Yang, Tao Sun
Vasculogenic mimicry (VM) formed by aggressive tumor cells to mimic vasculogenic networks plays an important role in the tumor malignancy of HCC. However, the pathogenesis underlying VM is complex and has not been fully defined. m6A is a common mRNA modification and has many biological effects. However, the relationship between m6A and VM remains unclear. In this research, we found that m6A methyltransferase METTL3 in HCC tissues was positively correlated with VM. The m6A level of mRNA significantly increased in 3D cultured cells treated with VEGFa and was related to VM formation...
September 13, 2020: Angiogenesis
Qing Li, Wei Hu, Wei-Xin Liu, Liu-Yang Zhao, Dan Huang, Xiao-Dong Liu, Hung Chan, Yuchen Zhang, Ju-Deng Zeng, Olabisi Oluwabukola Coker, Wei Kang, Simon Siu Man Ng, Lin Zhang, Sunny Hei Wong, Tony Gin, Matthew Tak Vai Chan, Jian-Lin Wu, Jun Yu, William Ka Kei Wu
BACKGROUND & AIMS: Streptococcus thermophilus was identified to be depleted in patients with colorectal cancer (CRC) by shotgun metagenomic sequencing of 526 multi-cohort fecal samples. Here, we aim to investigate if this bacterium could act as a prophylactics for CRC prevention. METHODS: The anti-tumor effects of S. thermophilus were assessed in cultured colonic epithelial cells and in two murine models of intestinal tumorigenesis. The tumor-suppressive protein produced by S...
September 10, 2020: Gastroenterology
Jing Xue, Wei Sang, Li-Ping Su, Hai-Xia Gao, Wen-Li Cui, Gulinaer Abulajiang, Qian Wang, Jing Zhang, Wei Zhang
Hub proteins related with Hippo signal pathway in glioma were investigated using proteomics methods (Tandem Mass Tag, TMT) to determine the differentially expressed proteins in glioblastoma (GBM). Ingenuity Pathway Analysis (IPA) was performed to complement proteomic findings by identifying the top canonical pathways as well as to suggest novel proteins for the targeted therapy of glioma. A total of 222 formalin-fixed paraffin-embedded (FFPE) glioma tissue samples were used to verify the expression of protein phosphatase 1γ (PP1γ), Yes-associated protein 1 (YAP1), and SOX2 via immunohistochemistry...
August 23, 2020: Pathology, Research and Practice
Xueke Lin, Dilu Feng, Ping Li, Yuchun Lv
Ovarian cancer is one of the most common gynecological cancers with high morbidity and mortality, which seriously endangers women's health and quality of life. Long noncoding RNAs (lncRNAs) can regulate the progression of cancers, including ovarian cancer. LINC00857 (long intergenic non-protein coding RNA 857) has been discovered to be a crucial factor in the regulation of cancer development. Nevertheless, the specific functions and mechanisms of LINC00857 in ovarian cancer remain unclear. The Hippo signaling pathway can involve in cancer progression...
September 12, 2020: Cancer Medicine
Walid J Azar, Elizabeth L Christie, Chris Mitchell, David S Liu, George Au-Yeung, David D L Bowtell
Ovarian clear cell adenocarcinoma (OCCA) is characterized by a particularly poor response to conventional chemotherapy and a short overall survival time in women with established disease. The development of targeted treatments for OCCA relies on a better understanding of its molecular characteristics. IL-6 is strongly expressed in OCCA and may therefore provide a novel therapeutic target. Here we use CRISPR/Cas9 and conditional short-hairpin interfering RNA to perform loss-of-function studies in human OCCA cell lines to explore the requirement for IL-6 in vitro and in vivo...
September 11, 2020: Cancer Research
Andrés Gambini, Matteo Duque Rodríguez, María Belén Rodríguez, Olinda Briski, Ana P Flores Bragulat, Natalia Demergassi, Luis Losinno, Daniel F Salamone
Several equids have gone extinct and many extant equids are currently considered vulnerable to critically endangered. This work aimed to evaluate whether domestic horse oocytes support preimplantation development of zebra embryos obtained by intracytoplasmic sperm injection (ICSI, zebroid) and cloning, and to study the Hippo signaling pathway during the lineage specification of trophectoderm cells and inner cell mass cells. We first showed that zebra and horse sperm cells induce porcine oocyte activation and recruit maternal SMARCA4 during pronuclear formation...
2020: PloS One
Qinghua Zou, Huifang Zhang, Fanliang Meng, Lihua He, Jianzhong Zhang, Di Xiao
BACKGROUND: The correlation between the infection of H. pylori and the occurrence of gastric MALT lymphoma (GML) has been well documented. However, the mechanism of how GML is caused by this bacterium is not well understood, although some immunologic mechanisms are thought to be involved. MATERIALS AND METHODS: In this study, we performed both transcriptomic and proteomic analyses on gastric cancer cells infected by H. pylori isolates from GML patients and the gastric ulcer strain 26695 to investigate the differentially expressed molecular signatures that were induced by GML isolates...
2020: PloS One
Dacheng Xie, Shijun Yu, Li Li, Ming Quan, Yong Gao
Both autotaxin (ATX) and Forkhead Box M1 (FOXM1) have been commonly recognized as oncogenes in multiple types of human malignancies. However, the expression and biological functions of ATX in pancreatic ductal adenocarcinoma (PDAC), and its correlation with FOXM1 are poorly understood. The present study aimed to investigate their correlation and biological consequences in PDAC development. By dual luciferase reporter and chromatin immunoprecipitation assays, we found that ATX was a downstream transcriptional target gene of FOXM1...
2020: American Journal of Translational Research
Bowen Wu, Yu Huang, Yingwan Luo, An Ma, Zhaoxing Wu, Yichao Gan, Ying Xu, Rongzhen Xu
Cell division cycle associated (CDCA) gene family plays an important role in cells. However, some researchers revealed that overexpression of CDCAs might contribute to the tumor progression in several cancers. Here, we analyzed the role of this gene family in hepatocellular carcinoma (HCC). We used several web tools and found that most of CDCAs were highly expressed in tumor tissues compared to the paracancer tissues in HCC. We then used RT-qPCR to confirm our results. The results showed that CDCA2, CDCA3, CDCA5 and CDCA8 were up-regulated in HCC...
2020: Journal of Cancer
Bryan King, Jingwen Araki, Wilhelm Palm, Craig B Thompson
The uptake of macromolecules and cellular debris through macropinocytosis has emerged as an important nutrient acquisition strategy of cancer cells. Genetic alterations commonly found in human cancers (e.g. mutations in KRAS or loss of PTEN) have been shown to increase macropinocytosis. To identify additional effectors that enable cell growth dependent on the uptake of extracellular proteins, pancreatic ductal adenocarcinoma (PDA) cells were selected for growth in medium where extracellular albumin was the obligate source of the essential amino acid leucine...
September 10, 2020: Genes & Development
Lin Hu, Jing Wang, Yunliang Wang, Linpeng Wu, Chao Wu, Bo Mao, E Maruthi Prasad, Yuhong Wang, Y Eugene Chin
BACKGROUND: LOX-like 1 (LOXL1) is a lysyl oxidase, and emerging evidence has revealed its effect on malignant cancer progression. However, its role in colorectal cancer (CRC) and the underlying molecular mechanisms have not yet been elucidated. METHODS: LOXL1 expression in colorectal cancer was detected by immunohistochemistry, western blotting and real-time PCR. In vitro, colony formation, wound healing, migration and invasion assays were performed to investigate the effects of LOXL1 on cell proliferation, migration and invasion...
September 10, 2020: Cell Communication and Signaling: CCS
Shuxia Gao, Yingchao Wang, Lijuan Ji
Human Hippo signaling pathway has been recognized as a new and promising therapeutic target of gastrointestinal cancers, which is regulated by the intermolecular recognition between the TEA domain (TEAD) transcription factor and its prime coactivators. The coactivator proteins adopt two hotspot sites, namely α-helix and Ω-loop, to interact with TEAD. Here, we demonstrate that both the α-helix and Ω-loop peptides cannot maintain in structured state when splitting from the full-length coactivator proteins; they exhibit a large intrinsic disorder in free state that prevents the coactivator peptide recognition by TEAD...
September 10, 2020: Journal of Receptor and Signal Transduction Research
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