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https://www.readbyqxmd.com/read/29332923/heart-failure-as-an-aging-related-phenotype
#1
Hiroyuki Morita, Issei Komuro
The molecular pathophysiology of heart failure, which is one of the leading causes of mortality, is not yet fully understood. Heart failure can be regarded as a systemic syndrome of aging-related phenotypes. Wnt/β-catenin signaling and the p53 pathway, both of which are key regulators of aging, have been demonstrated to play a critical role in the pathogenesis of heart failure. Circulating C1q was identified as a novel activator of Wnt/β-catenin signaling, promoting systemic aging-related phenotypes including sarcopenia and heart failure...
January 15, 2018: International Heart Journal
https://www.readbyqxmd.com/read/29258822/lncrna-malat1-regulates-oxldl-induced-cd36-expression-via-activating-%C3%AE-catenin
#2
Ning Huangfu, Zhenyu Xu, Wenyuan Zheng, Yong Wang, Jingsong Cheng, Xiaomin Chen
The expression of scavenger receptors in macrophages regulating lipid uptake plays an important role in foam cell formation and the subsequent atherosclerotic plaque formation. Long non-coding RNA MALAT1 is abundantly expressed in THP-1-derived macrophages, and oxidized low-density lipoprotein promotes its transcription by qRT-PCR and RNA FISH detection. Through chemical inhibitor treatments and by performing a dual luciferase reporter analysis, we found that oxLDL induces MALAT1 transcription through the NF-κB pathway...
December 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29217140/inhibition-of-canonical-wnt-signaling-pathway-by-%C3%AE-catenin-cbp-inhibitor-icg-001-ameliorates-liver-fibrosis-in-vivo-through-suppression-of-stromal-cxcl12
#3
Büsra Öztürk Akcora, Gert Storm, Ruchi Bansal
Quiescent hepatic stellate cells (HSCs), in response to liver injury, undergo characteristic morphological transformation into proliferative, contractile and ECM-producing myofibroblasts. In this study, we investigated the implication of canonical Wnt signaling pathway in HSCs and liver fibrogenesis. Canonical Wnt signaling pathway activation and inhibition using β-catenin/CBP inhibitor ICG001 was examined in-vitro in TGFβ-activated 3T3, LX2, primary human HSCs, and in-vivo in CCl4-induced acute liver injury mouse model...
December 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29191973/blocking-the-feedback-loop-between-neuroendocrine-differentiation-and-macrophages-improves-the-therapeutic-effects-of-enzalutamide-mdv3100-on-prostate-cancer
#4
Chao Wang, Guang Peng, Hai Huang, Fei Liu, De-Pei Kong, Ke-Qin Dong, Li-He Dai, Zhe Zhou, Kai-Jian Wang, Jun Yang, Yan-Qiong Cheng, Xu Gao, Min Qu, Hongru Wang, Feng Zhu, Qin-Qin Tian, Dan Liu, Li Cao, Xingang Cui, Chuanliang Xu, Dan-Feng Xu, Yinghao Sun
PURPOSE: Androgen-deprivation therapy (ADT), including enzalutamide, induces resistance in prostate cancer (PCa); ADT resistance is associated with neuroendocrine differentiation (NED) and tumor-associated macrophages (TAMs). This study aimed to investigate the association between enzalutamide-induced NED and TAMs and its mechanism. EXPERIMENTAL DESIGN: The association between enzalutamide-induced NED and TAMs was investigated by immunohistochemistry using PCa tissues, enzalutamide-resistant mouse xenografts and a co-culture system...
November 30, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29140564/%C3%AE-catenin-and-il-1%C3%AE-dependent-cxcl10-production-drives-progression-of-disease-in-a-mouse-model-of-congenital-hepatic-fibrosis
#5
Eleanna Kaffe, Romina Fiorotto, Francesca Pellegrino, Valeria Mariotti, Mariangela Amenduni, Massimiliano Cadamuro, Luca Fabris, Mario Strazzabosco, Carlo Spirli
Congenital Hepatic Fibrosis (CHF), a genetic disease caused by mutations in the PKHD1 gene, encoding for the protein fibrocystin (FPC), is characterized by biliary dysgenesis, progressive portal fibrosis, and by a PKA-mediated activating phosphorylation of β-Catenin at Ser675. Biliary structures of Pkhd1(del4/del4) mice, a mouse model of CHF, secrete CXCL10 a chemokine able to recruit macrophages. The aim of this study is to clarify whether CXCL10 plays a pathogenetic role in disease progression in CHF/CD and to understand the mechanisms leading to increased CXCL10 secretion...
November 15, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29137395/lithium-chloride-inhibits-titanium-particle-induced-osteoclastogenesis-by-inhibiting-the-nf-%C3%AE%C2%BAb-pathway
#6
Xuanyang Hu, Zhirong Wang, Jiawei Shi, Xiaobin Guo, Liangliang Wang, Zichuan Ping, Yunxia Tao, Huilin Yang, Jun Zhou, Yaozeng Xu, Dechun Geng
Osteoclast over-activation and inflammation responses promote peri-implant osteolysis (PIO), which is the leading cause of aseptic artificial joint loosening. We examined the effect of lithium chloride (LiCl) on wear debris-induced osteoclastogenesis and inflammation. Fifty-Six C57BL/6J male mice were randomly distributed into four groups: sham control (sham, treated with phosphate buffered saline [PBS]), vehicle (treated with titanium/PBS), low-LiCl (L-LiCl, titanium: 50 mg/kg LiCl) and high-LiCl (H-LiCl, titanium: 200 mg/kg LiCl)...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29084211/sparcl1-suppresses-osteosarcoma-metastasis-and-recruits-macrophages-by-activation-of-canonical-wnt-%C3%AE-catenin-signaling-through-stabilization-of-the-wnt-receptor-complex
#7
S-J Zhao, Y-Q Jiang, N-W Xu, Q Li, Q Zhang, S-Y Wang, J Li, Y-H Wang, Y-L Zhang, S-H Jiang, Y-J Wang, Y-J Huang, X-X Zhang, G-A Tian, C-C Zhang, Y-Y Lv, M Dai, F Liu, R Zhang, D Zhou, Z-G Zhang
Metastasis significantly reduces the survival rate of osteosarcoma (OS) patients. Therefore, identification of novel targets remains extremely important to prevent metastasis and treat OS. In this report, we show that SPARCL1 is downregulated in OS by epigenetic methylation of promoter DNA. In vitro and in vivo experiments revealed that SPARCL1 inhibits OS metastasis. We further demonstrated that SPARCL1-activated WNT/β-catenin signaling by physical interaction with various frizzled receptors and lipoprotein receptor-related protein 5/6, leading to WNT-receptor complex stabilization...
October 30, 2017: Oncogene
https://www.readbyqxmd.com/read/29079416/macrophage-migration-inhibitory-factor-promotes-tumor-aggressiveness-of-esophageal-squamous-cell-carcinoma-via-activation-of-akt-and-inactivation-of-gsk3%C3%AE
#8
Rui-Min Liu, Dan-Ni Sun, Ye-Lin Jiao, Pan Wang, Juan Zhang, Ming Wang, Jin Ma, Man Sun, Bian-Li Gu, Pan Chen, Ke Liu, Heng Ma, She-Gan Gao, Yuan-Fang Ma, Yi-Jun Qi
The pleiotropic pro-inflammatory cytokine, macrophage migration inhibitory factor (MIF), represents an important link between chronic inflammation and tumorigenesis. Although accumulating evidence demonstrates that MIF overexpression is implicated in the development and progression of multiple cancers, including esophageal squamous cell carcinoma (ESCC), the molecular mechanisms underlying its tumor-promoting roles in ESCC remain unclear. In the present study, we observed that MIF is overexpressed in ESCC and correlated significantly with lymph node metastasis, advanced clinical stage, and poor survival of ESCC...
October 25, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29066299/%C3%AE-elemene-attenuates-macrophage-activation-and-proinflammatory-factor-production-via-crosstalk-with-wnt-%C3%AE-catenin-signaling-pathway
#9
Yangyi Fang, Yanhua Kang, Han Zou, Xiaxuan Cheng, Tian Xie, Liyun Shi, Hang Zhang
β-elemene, extracted from Rhizoma zedoariae, has been widely used as a traditional medicine for its antitumor activity against a broad range of cancers. However, the effect of β-elemene in inflammation disorders has yet to be determined. The present study was designed to investigate the anti-inflammatory effects and potential molecular mechanisms of β-elemene in lipopolysaccharide (LPS)-induced murine macrophage cells RAW264.7. We found that the production of pro-inflammatory mediators, including interleukin-6(IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), induced by LPS was significantly suppressed by β-elemene in a dose-dependent manner in RAW264...
October 21, 2017: Fitoterapia
https://www.readbyqxmd.com/read/29021383/wnt-%C3%AE-catenin-promoted-macrophage-alternative-activation-contributes-to-kidney-fibrosis
#10
Ye Feng, Jiafa Ren, Yuan Gui, Wei Wei, Bingyan Shu, Qingmiao Lu, Xian Xue, Xiaoli Sun, Weichun He, Junwei Yang, Chunsun Dai
The Wnt/β-catenin pathway is crucial in normal development and throughout life, but aberrant activation of this pathway has been linked to kidney fibrosis, although the mechanisms involved remain incompletely determined. Here, we investigated the role of Wnt/β-catenin in regulating macrophage activation and the contribution thereof to kidney fibrosis. Treatment of macrophages with Wnt3a exacerbated IL-4- or TGFβ1-induced macrophage alternative (M2) polarization and the phosphorylation and nuclear translocation of STAT3 in vitro Conversely, inhibition of Wnt/β-catenin signaling prevented these IL-4- or TGFβ1-induced processes...
October 11, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28935467/reciprocal-role-of-sirt6-and-hexokinase-2-in-the-regulation-of-autophagy-driven-monocyte-differentiation
#11
Ankita Singh, Ellora Sen
Emerging evidences suggest the impact of autophagy on differentiation but the underlying molecular links between metabolic restructuring and autophagy during monocyte differentiation remain elusive. An increase in PPARγ, HK2 and SIRT6 expression was observed upon PMA induced monocyte differentiation. While PPARγ positively regulated HK2 and SIRT6 expression, the latter served as a negative regulator of HK2. Changes in expression of these metabolic modelers were accompanied by decreased glucose uptake and increase in Chibby, a potent antagonist of β-catenin/Wnt pathway...
November 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28867647/inhibitory-effects-of-melatonin-on-titanium-particle-induced-inflammatory-bone-resorption-and-osteoclastogenesis-via-suppression-of-nf-%C3%AE%C2%BAb-signaling
#12
Zichuan Ping, Zhirong Wang, Jiawei Shi, Liangliang Wang, Xiaobin Guo, Wei Zhou, Xuanyang Hu, Xiexing Wu, Yu Liu, Wen Zhang, Huilin Yang, Yaozeng Xu, Ye Gu, Dechun Geng
Wear debris-induced peri-implant osteolysis challenges the longevity of implants. The host response to wear debris causes chronic inflammation, promotes bone resorption, and impairs bone formation. We previously demonstrated that melatonin enhances bone formation and attenuates wear debris-induced bone loss in vivo. However, whether melatonin inhibits chronic inflammation and bone resorption at sites of wear debris-induced osteolysis remains unclear. In this study, we examined the potential inhibitory effects of melatonin on titanium particle-induced inflammatory osteolysis in a murine calvarial model and on RANKL-induced osteoclastic formation in bone marrow-derived macrophages...
September 1, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28837884/macrophages-induce-emt-to-promote-invasion-of-lung-cancer-cells-through-the-il-6-mediated-cox-2-pge2-%C3%AE-catenin-signalling-pathway
#13
Dehai Che, Shuai Zhang, Zihan Jing, Lihua Shang, Shi Jin, Fang Liu, Jing Shen, Yue Li, Jing Hu, Qingwei Meng, Yan Yu
Infiltration of macrophages plays a critical role in the connection between inflammation and cancer invasion; however, the molecular mechanism that enables this crosstalk remains unclear. This paper investigates a molecular link between infiltration of macrophages and metastasis of lung cancer cells. In this study, the macrophage density and cyclooxygenase-2 (COX-2) protein were examined in surgical specimens by immunohistochemistry (IHC), and the prostaglandin E2 (PGE2) levels were determined in the blood of 30 non-small cell lung cancer (NSCLC) patients using enzyme-linked immunosorbent assay (ELISA)...
October 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28835626/mitigation-of-sepsis-induced-inflammatory-responses-and-organ-injury-through-targeting-wnt-%C3%AE-catenin-signaling
#14
Archna Sharma, Weng-Lang Yang, Mahendar Ochani, Ping Wang
The Wnt/β-catenin pathway has been involved in regulating inflammation in various infectious and inflammatory diseases. Sepsis is a life-threatening condition caused by dysregulated inflammatory response to infection with no effective therapy available. Recently elevated Wnt/β-catenin signaling has been detected in sepsis. However, its contribution to sepsis-associated inflammatory response remains to be explored. In this study, we show that inhibition of Wnt/β-catenin signaling reduces inflammation and mitigates sepsis-induced organ injury...
August 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28749946/genome-wide-association-analysis-identifies-genetic-correlates-of-immune-infiltrates-in-solid-tumors
#15
Nathan O Siemers, James L Holloway, Han Chang, Scott D Chasalow, Petra B Ross-MacDonald, Charles F Voliva, Joseph D Szustakowski
Therapeutic options for the treatment of an increasing variety of cancers have been expanded by the introduction of a new class of drugs, commonly referred to as checkpoint blocking agents, that target the host immune system to positively modulate anti-tumor immune response. Although efficacy of these agents has been linked to a pre-existing level of tumor immune infiltrate, it remains unclear why some patients exhibit deep and durable responses to these agents while others do not benefit. To examine the influence of tumor genetics on tumor immune state, we interrogated the relationship between somatic mutation and copy number alteration with infiltration levels of 7 immune cell types across 40 tumor cohorts in The Cancer Genome Atlas...
2017: PloS One
https://www.readbyqxmd.com/read/28729694/paracrine-cyclooxygenase-2-activity-by-macrophages-drives-colorectal-adenoma-progression-in-the-apc-min-mouse-model-of-intestinal-tumorigenesis
#16
Mark A Hull, Richard J Cuthbert, C W Stanley Ko, Daniel J Scott, Elizabeth J Cartwright, Gillian Hawcroft, Sarah L Perry, Nicola Ingram, Ian M Carr, Alexander F Markham, Constanze Bonifer, P Louise Coletta
Genetic deletion or pharmacological inhibition of cyclooxygenase (COX)-2 abrogates intestinal adenoma development at early stages of colorectal carcinogenesis. COX-2 is localised to stromal cells (predominantly macrophages) in human and mouse intestinal adenomas. Therefore, we tested the hypothesis that paracrine Cox-2-mediated signalling from macrophages drives adenoma growth and progression in vivo in the Apc (Min/+) mouse model of intestinal tumorigenesis. Using a transgenic C57Bl/6 mouse model of Cox-2 over-expression driven by the chicken lysozyme locus (cLys-Cox-2), which directs integration site-independent, copy number-dependent transgene expression restricted to macrophages, we demonstrated that stromal macrophage Cox-2 in colorectal (but not small intestinal) adenomas from cLys-Cox-2 x Apc (Min/+) mice was associated with significantly increased tumour size (P = 0...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28723729/wnt-signaling-in-cardiovascular-disease-opportunities-and-challenges
#17
Austin Gay, Dwight A Towler
PURPOSE OF REVIEW: Cardiometabolic diseases increasingly afflict our aging, dysmetabolic population. Complex signals regulating low-density lipoprotein receptor-related protein (LRP) and frizzled protein family members - the plasma membrane receptors for the cadre of Wnt polypeptide morphogens - contribute to the control of cardiovascular homeostasis. RECENT FINDINGS: Both canonical (β-catenin-dependent) and noncanonical (β-catenin-independent) Wnt signaling programs control vascular smooth muscle (VSM) cell phenotypic modulation in cardiometabolic disease...
October 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28714032/atf3-promotes-migration-and-m1-m2-polarization-of-macrophages-by-activating-tenascin%C3%A2-c-via-wnt-%C3%AE-%C3%A2-catenin-pathway
#18
Hao Sha, Dianzhong Zhang, Yunfei Zhang, Yanhua Wen, Yucai Wang
There are different polarization states of macrophages, including the classically activated M1 phenotype and the alternatively activated M2 phenotype. These have different functions in the inflammation process. Activating transcription factor 3 (ATF3) is a key transcriptional regulator that inhibits the inflammatory response. However, the effects of ATF3 on migration and anti‑inflammatory control mechanisms of macrophages have not been thoroughly investigated. The present study investigated the effect of ATF3 on macrophage migration and M1/M2 polarization...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28671671/wnt-%C3%AE-catenin-activation-and-macrophage-induction-during-liver-cancer-development-following-steatosis
#19
A Debebe, V Medina, C-Y Chen, I M Mahajan, C Jia, D Fu, L He, N Zeng, B W Stiles, C-L Chen, M Wang, K-R Aggarwal, Z Peng, J Huang, J Chen, M Li, T Dong, S Atkins, Z Borok, W Yuan, K Machida, C Ju, M Kahn, D Johnson, B L Stiles
Obesity confers an independent risk for carcinogenesis. In the liver, steatosis often proceeds cancer formation; however, the mechanisms by which steatosis promotes carcinogenesis is unknown. We hypothesize that steatosis alters the microenvironment to promote proliferation of tumor initiating cells (TICs) and carcinogenesis. We used several liver cancer models to address the mechanisms underlying the role of obesity in cancer and verified these findings in patient populations. Using bioinformatics analysis and verified by biochemical assays, we identified that hepatosteatosis resulting from either Pten deletion or transgenic expression of HCV core/NS5A proteins, promotes the activation of Wnt/β-catenin...
October 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28615615/stat6-upregulation-promotes-m2-macrophage-polarization-to-suppress-atherosclerosis
#20
Min Gong, Xiaozhen Zhuo, Aiqun Ma
BACKGROUND Macrophages are highly heterogeneous and plastic cells that are involved in all stages of atherogenesis. They can undergo polarization by shifting between M1 and M2 functional phenotypes. However, the role of macrophage polarization and the molecular mechanism in modulating atherosclerotic plaque stability remain incompletely understood. Our study investigated the role of STAT6 in regulating macrophage phenotypes to affect atherosclerotic plaque stability. MATERIAL AND METHODS A murine atherosclerosis model with vulnerable plaques was induced with high-cholesterol diet and PCCP surgeries in ApoE-/- mice...
June 15, 2017: Medical Science Monitor Basic Research
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