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Xiaoling Wu, Jiamei Zhang, Chenjie Ma, Wu Li, Jin Zeng, Yujiong Wang, Guangcun Deng
Mycobacterium tuberculosis (Mtb)-induced autophagy of alveolar macrophages has been confirmed to play a central role in the pathogenesis of tuberculosis. Growing evidence indicates that excessive or uncontrolled autophagic activity, which results in type II programmed cell death, can be regulated by many factors, including Wnt/β-catenin signalling. Wnt/β-catenin signalling has been demonstrated to be involved in multiple diseases through the regulation of autophagy; however, its exact role in regulating autophagy induced by Mtb remains unclear...
December 11, 2018: Microbial Pathogenesis
Bethan A Brown, Georgia M Connolly, Carina E J Mill, Helen Williams, Gianni D Angelini, Jason L Johnson, Sarah J George
We previously reported pro-survival effects of Wnt3a and Wnt5a proteins in vascular smooth muscle cells (VSMCs). Wnt5a achieved this through induction of Wnt1-inducible signalling pathway protein-1 (WISP-1) consequent to β-catenin/CREB-dependent, TCF-independent, signalling. However, we found that as atherosclerosis advances, although Wnt5a protein was increased, WISP-1 was reduced. We hypothesized this disconnect could be due to aging. In this study, we elucidate the mechanism underlying Wnt3a pro-survival signalling and demonstrate the differential effect of age on Wnt3a- and Wnt5a-mediated survival...
December 12, 2018: Aging Cell
H Song, H-N Lu, X Chen, X-F Jiang, Y Yang, J Feng
OBJECTIVE: To explore whether miR-216a-3p could promote differentiation of bone marrow mesenchymal stem cells (BMMSCs) into type II alveolar epithelial cells (ACE II) via Wnt/β-catenin pathway, thereby alleviating neonatal respiratory distress syndrome (NRDS). MATERIALS AND METHODS: BMMSCs were directionally differentiated into ACE II cells. Expressions of ACE II cell-specific transcription factors Occludin, KGF, CK18, SpA, SpB, and SpC were detected at the different time points after cell differentiation...
November 2018: European Review for Medical and Pharmacological Sciences
Jazmín Calyeca, Yalbi I Balderas-Martínez, Raúl Olmos, Rogelio Jasso, Vilma Maldonado, Quetzali Rivera, Moisés Selman, Annie Pardo
Idiopathic pulmonary fibrosis is a devastating aging-associated disease of unknown etiology. Despite that aging is a major risk factor, the mechanisms linking aging with this disease are uncertain, and experimental models to explore them in lung fibrosis are scanty. We examined the fibrotic response to bleomycin-induced lung injury in Zmpste24-deficient mice, which exhibit nuclear lamina defects developing accelerated aging. We found that young WT and Zmpste24(-/-) mice developed a similar fibrotic response to bleomycin...
December 10, 2018: Aging
Guixing Zhang, Mingyue Ge, Ziwei Han, Sheng Wang, Jiangwen Yin, Li Peng, Feng Xu, Qingtong Zhang, Zhigang Dai, Liping Xie, Yan Li, Junqiang Si, Ketao Ma
AIM: The Wnt/β-catenin signaling pathway plays an important role in ischemia-reperfusion(I/R) injury, and the transforming growth factor(TGF)-β/Smad signaling pathway participates in the neuroprotection effect induced by isoflurane(ISO) postconditioning. In this study, we aimed to explore the role of the Wnt/|[beta]|-catenin β-catenin signaling pathway in the neuroprotection effect induced by ISO postconditioning, and investigate the interaction of Wnt/β-catenin and TGF-β/Smad signaling pathway in this neuroprotection effect...
December 5, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Takumi Hiraiwa, Yuichiro Nakai, Takahiro G Yamada, Ryuichi Tanimoto, Hiroshi Kimura, Yoshinori Matsumoto, Norihisa Miki, Noriko Hiroi, Akira Funahashi
Proper determination of the cell division axis is essential during development. Wnt3a is a known regulator of the cell division axis; however, the sensitivity of cells to Wnt3a signalling and its role in determining the cell division axis have not been measured to date. To address this gap, we took advantage of the asymmetric distribution of outer dense fibre 2 (ODF2/cenexin) proteins on centrosomes in dividing cells. To precisely quantify the sensitivity of cells to Wnt3a signalling, we developed a microfluidic cell culture device, which can produce a quantitative gradient of signalling molecules...
December 2018: FEBS Open Bio
Shengcai Qi, Pengfei Zhang, Ming Ma, Minghua Yao, Jinjin Wu, Ermei Mäkilä, Jarno Salonen, Heikki Ruskoaho, Yuanzhi Xu, Hélder A Santos, Hongbo Zhang
Nanotechnology employs multifunctional engineered materials in the nanoscale range that provides many opportunities for translational stem cell research and therapy. Here, a cell-penetrating peptide (virus-1 transactivator of transcription)-conjugated, porous silicon nanoparticle (TPSi NP) loaded with the Wnt3a protein to increase both the cell survival rate and the delivery precision of stem cell transplantation via a combinational theranostic strategy is presented. The TPSi NP with a pore size of 10.7 nm and inorganic framework enables high-efficiency loading of Wnt3a, prolongs Wnt3a release, and increases antioxidative stress activity in the labeled mesenchymal stem cells (MSCs), which are highly beneficial properties for cell protection in stem cell therapy for myocardial infarction...
November 28, 2018: Small
Raven Diacou, Yilin Zhao, Deyou Zheng, Ales Cvekl, Wei Liu
Gene regulation of multipotent neuroretinal progenitors is partially understood. Through characterizing Six3 and Six6 double knockout retinas (DKOs), we demonstrate Six3 and Six6 are jointly required for the maintenance of multipotent neuroretinal progenitors. Phenotypes in DKOs were not found in either Six3 nulls or Six6 nulls. At the far periphery, ciliary margin (CM) markers Otx1 and Cdon together with Wnt3a and Fzd1 were ectopically upregulated, whereas neuroretinal progenitor markers Sox2, Notch1, and Otx2 were absent or reduced...
November 27, 2018: Cell Reports
Jingrong Li, Ruihua Fang, Jianqin Wang, Liehua Deng
Malignant melanoma is an aggressive skin cancer with a high mortality rate. Nucleolar protein 14 (NOP14) has been implicated in cancer development. However, the role of NOP14 in malignant melanoma progression remains largely unclear. In this study, we observed that malignant melanoma tissue showed NOP14 down-regulation compared to melanocytic nevi tissues. Moreover, we observed that NOP14 expression was significantly associated with melanoma tumor thickness and lymph node metastasis. NOP14 overexpression in melanoma cells suppressed proliferation, caused G1 phase arrest, promoted apoptosis, and inhibited melanoma cell migration and invasion...
November 23, 2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Tangzhao Liang, Wenling Gao, Lei Zhu, Jianhua Ren, Hui Yao, Kun Wang, Dehai Shi
This study aimed to evaluate the effect of tissue inhibitor of metalloproteinase-1 (TIMP-1) on the proliferation and osteogenic differentiation potential of human bone marrow-derived MSCs (hBMSCs). hBMSCs with stable TIMP-1 overexpression or TIMP-1 knockdown were generated. Osteogenic differentiation was assessed by Alizarin Red S staining, alkaline phosphatase (ALP) activity and expression of specific markers. Compared to the vehicle controls, TIMP-1 knockdown significantly promoted the growth of hBMSCs. TIMP-1 knockdown up-regulated β-catenin and cyclin D1 proteins...
November 25, 2018: Bioscience Reports
Ryosuke Negoro, Kazuo Takayama, Kanae Kawai, Kazuo Harada, Fuminori Sakurai, Kazumasa Hirata, Hiroyuki Mizuguchi
The small intestine plays an important role in the absorption and metabolism of oral drugs. In the current evaluation system, it is difficult to predict the precise absorption and metabolism of oral drugs. In this study, we generated small intestinal epithelial-like cells from human induced pluripotent stem cells (hiPS-SIECs), which could be applied to drug absorption and metabolism studies. The small intestinal epithelial-like cells were efficiently generated from human induced pluripotent stem cell by treatment with WNT3A, R-spondin 3, Noggin, EGF, IGF-1, SB202190, and dexamethasone...
November 13, 2018: Stem Cell Reports
Rose K Davidson, Jonathan Green, Sarah Gardner, Yongping Bao, Aedin Cassidy, Ian M Clark
Osteoarthritis (OA) is a multifactorial disease and nutrition is a modifiable factor that may contribute to disease onset or progression. A detailed understanding of mechanisms through which diet-derived bioactive molecules function and interact in OA is needed. We profiled 96 diet-derived, mainly plant-based bioactives using an in vitro model in chondrocytes, selecting four candidates for further study. We aimed to determine synergistic interactions between bioactives that affected the expression of key genes in OA...
November 21, 2018: Scientific Reports
Juanjuan Li, Yun Zhang, Kechun Liu, Qiuxia He, Chen Sun, Jian Han, Liwen Han, Qingping Tian
The aim of the study was to determine the developmental toxicity of the traditional Chinese medicine Xiaoaiping (XAP) and to investigate its underlying mechanism of action. Zebrafish embryos were incubated with 0.4, 0.8, 1.2, and 1.6 mg/mL XAP. Endpoints such as mortality, hatching rate, malformation, body length, morphology score, swimming behavior, histological changes, reactive oxygen species (ROS) production, total superoxide dismutase (T-SOD) activity, and the mRNA expression of genes related to oxidative stress, endoplasmic reticulum (ER) stress, apoptosis, and the Wnt pathway were evaluated...
2018: Frontiers in Pharmacology
Hiroko Ida-Yonemochi, Wataru Morita, Nobuo Sugiura, Ryosuke Kawakami, Yuki Morioka, Yuka Takeuchi, Toshiya Sato, Shunichi Shibata, Hideto Watanabe, Takeshi Imamura, Michihiro Igarashi, Hayato Ohshima, Kosei Takeuchi
Chondroitin sulfate (CS) proteoglycan is a major component of the extracellular matrix and plays an important part in organogenesis. To elucidate the roles of CS for craniofacial development, we analyzed the craniofacial morphology in CS N-acetylgalactosaminyltransferase-1 (T1) gene knockout (KO) mice. T1KO mice showed the impaired intramembranous ossification in the skull, and the final skull shape of adult mice included a shorter face, higher and broader calvaria. Some of T1KO mice exhibited severe facial developmental defect, such as eye defects and cleft lip and palate, causing embryonic lethality...
November 20, 2018: Scientific Reports
Qiu Peng, Ling Chen, Wei Wu, Jia Wang, Xiang Zheng, Zihua Chen, Qin Jiang, Jiaqi Han, Lingyu Wei, Lujuan Wang, Jin Huang, Jian Ma
The erythropoietin-producing hepatoma (EPH) receptor A2 (EphA2) belongs to the Eph family of receptor tyrosine kinases. EphA2 is highly correlated with the formation of many solid tumors and has been linked to the dysregulation of signaling pathways that promote tumor cell proliferation, migration, and invasion as well as angiogenesis. Deregulation of Wnt signaling is implicated in many forms of human disease including gastric cancer. We previously reported that EphA2 promotes the epithelial-mesenchymal transition through Wnt/β-catenin signaling in gastric cancer...
November 19, 2018: Cell Death & Disease
Hui Xu, Xingai Jiao, Yilei Wu, Shuo Li, Lili Cao, Liang Dong
Fine particulate matter (PM2.5) is associated with an increased lung cancer risk. However, the effect of PM2.5 exposure on lung cancer cells is still largely unknown. The present study revealed that A549 lung cancer cells secreted exosomes containing high levels of Wnt3a after treatment with PM2.5. These exosomes activated β‑catenin signalling in A549 cells. These exosomes exhibited no effects on migration and invasion, but promoted proliferation of A549 cells via the Wnt3a/β‑catenin pathway in vitro...
November 9, 2018: Oncology Reports
Run-Bao Yang, Feng-Fei Lin, Jun Yang, Bin Chen, Ming-Hua Zhang, Qiao-Ping Lu, Bo Xiao, Yan Liu, Ke Zheng, Yong-Rong Qiu
PURPOSE: Osteoporosis is a condition characterized by decreased bone density and bone strength, commonly observed among older individuals. Caveolin-3 (CAV3) is a principal structural protein of the caveolae membrane domains, which has been reported to participate in cell signaling as well as the maintenance of cell structure. The aim of the current study was to investigate the effects involved with the silencing of CAV3 on bone formation among osteoporotic rat models via the Wnt signaling pathway...
November 14, 2018: Endocrine
Daniela N Rolph, Moonmoon Deb, Suman Kanji, Carl J Greene, Manjusri Das, Matthew Joseph, Reeva Aggarwal, Binnaz Leblebicioglu, Hiranmoy Das
Osteoporosis is a silent systemic disease that causes bone deterioration, and affects over 10 million people in the US alone. This study was undertaken to develop a potential stem cell therapy for osteoporosis. We have isolated and expanded human dental pulp-derived stem cells (DPSCs), characterized them, and confirmed their multipotential differentiation abilities. Stem cells often remain quiescent and require activation to differentiate and function. Herein, we show that ferutinin activates DPSCs by modulating the Wnt/β-catenin signaling pathway and key osteoblast-secreted proteins osteocalcin and collagen 1A1 both mRNA and protein levels...
November 6, 2018: Biochimica et biophysica acta. Molecular basis of disease
Ziru Li, Shiying Liu, Jianing Lou, Michael W Mulholland, Weizhen Zhang
Leucine-rich repeat G-protein-coupled receptors (LGRs) and their endogenous ligands R-spondin1-4 (Rspo) are critical in embryonic development and in maintenance of stem cells. The functions of the Rspo-LGR system in differentiated cells remain uncharacterized. In this study, the expression profiles of LGRs and Rspos were characterized in mature hepatocytes. A liver-specific knockout of LGR4 in mouse was generated and used to study hepatic ischemia and reperfusion induced injury (HIRI) as well as LPS/D-Gal induced liver injury...
November 8, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Yuan Luo, Yingdi Zhang, Guojun Miao, Yiwen Zhang, Yuehua Liu, Yuanliang Huang
OBJECTIVE: Bone marrow stem cells (BMSCs) can commit to both adipocyte and osteoblast lineages. However, the mechanism underlying how transcription factors regulate this process remains elusive. Our aims were to determine the role of runt-related transcription factor 1 (Runx1) in BMSCs lineage determination and the underlying mechanisms. STUDY DESIGN: BMSCs from mouse femur bone marrow were harvested and cultured in osteogenic medium. Runx1 was knocked down in BMSCs using lentivirus...
October 29, 2018: Archives of Oral Biology
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