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Source: Journal of Cellular and Molecular Medicine

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Total 94 results found since Jan 2013.

Placental growth factor silencing ameliorates liver fibrosis and angiogenesis and inhibits activation of hepatic stellate cells in a murine model of chronic liver disease
This study aimed to assess the effect of reducing PlGF expression using small interfering RNA (siRNA) on experimental liver fibrosis and angiogenesis, and to elucidate the underlying molecular mechanisms. Fibrosis was induced in mice by carbon tetrachloride (CCl4) for 8 weeks, and mice were treated with PlGF siRNA or non‐targeting control siRNA starting two weeks after initiating CCl4 injections. The results showed that PlGF was highly expressed in cirrhotic human and mice livers; which mainly distributed in activated hepatic stellate cells (HSCs). PlGF silencing robustly reduced liver inflammation, fibrosis, intrahepati...
Source: Journal of Cellular and Molecular Medicine - April 1, 2017 Category: Molecular Biology Authors: Xi Li, Qun ‐Yan Yao, Hong‐Chun Liu, Qian‐Wen Jin, Bei‐Li Xu, Shun‐Cai Zhang, Chuan‐Tao Tu Tags: Original Article Source Type: research

Chinese 1 strain of Toxoplasma gondii excreted –secreted antigens negatively modulate Foxp3 via inhibition of the TGFßRII/Smad2/Smad3/Smad4 pathway
This study was designed to investigate the effect of excreted–secreted antigens (ESA) of Chinese 1 strain of T. gondii on the expression of forkhead box transcription factor (Foxp3) as it pertains to early pregnancy and abortion. ESA caused a marked inhibition in the expression of Foxp3 both in vivo and in vitro. In addition, ESA negatively modulated Smad2 and Smad3 at the posttranslational level. Smad2 siRNA cooperated with ESA to further suppress the level of Foxp3. This inhibitory effect on Foxp3 expression was partially abrogated by overexpression of Smad2, Smad3 and Smad4. Additionally, ESA attenuated the expression...
Source: Journal of Cellular and Molecular Medicine - March 15, 2017 Category: Molecular Biology Authors: Jinling Chen, Caiqun Huang, Dandan Zhu, Pei Shen, Yinong Duan, Jianxin Wang, Chunzhao Yang, Liting Wu Tags: Original Article Source Type: research

Histone deacetylase inhibitors promote eNOS expression in vascular smooth muscle cells and suppress hypoxia ‐induced cell growth
Abstract Hypoxia stimulates excessive growth of vascular smooth muscle cells (VSMCs) contributing to vascular remodelling. Recent studies have shown that histone deacetylase inhibitors (HDIs) suppress VSMC proliferation and activate eNOS expression. However, the effects of HDI on hypoxia‐induced VSMC growth and the role of activated eNOS in VSMCs are unclear. Using an EdU incorporation assay and flow cytometry analysis, we found that the HDIs, butyrate (Bur) and suberoylanilide hydroxamic acid (SAHA) significantly suppressed the proliferation of hypoxic VSMC lines and induced apoptosis. Remarkable induction of cleaved ca...
Source: Journal of Cellular and Molecular Medicine - March 6, 2017 Category: Molecular Biology Authors: Xiaoling Tan, Lan Feng, Xiaoyong Huang, Yidong Yang, Chengzhong Yang, Yuqi Gao Tags: Original Article Source Type: research

Qiliqiangxin protects against anoxic injury in cardiac microvascular endothelial cells via NRG ‐1/ErbB‐PI3K/Akt/mTOR pathway
This study aims to investigate whether QL could protect CMECs against anoxic injury and to explore related signalling mechanisms. CMECs were successfully cultured from Sprague‐Dawley rats and exposed to anoxia for 12 hrs in the absence and presence of QL. Cell migration assay and capillary‐like tube formation assay on Matrigel were performed, and cell apoptosis was determined by TUNEL assay and caspase‐3 activity. Neuregulin‐1 (NRG‐1) siRNA and LY294002 were administrated to block NRG‐1/ErbB and PI3K/Akt signalling, respectively. As a result, anoxia inhibited cell migration, capillary‐like tube formation and ...
Source: Journal of Cellular and Molecular Medicine - February 28, 2017 Category: Molecular Biology Authors: Jingfeng Wang, Jingmin Zhou, Yanyan Wang, Chunjie Yang, Mingqiang Fu, Jingjing Zhang, Xueting Han, Zhiming Li, Kai Hu, Junbo Ge Tags: Original Article Source Type: research

3D culture increases pluripotent gene expression in mesenchymal stem cells through relaxation of cytoskeleton tension
Abstract Three‐dimensional (3D) culture has been shown to improve pluripotent gene expression in mesenchymal stem cells (MSCs), but the underlining mechanisms were poorly understood. Here, we found that the relaxation of cytoskeleton tension of MSCs in 3D culture was critically associated with the expressional up‐regulation of Nanog. Cultured in spheroids, MSCs showed decreased integrin‐based cell–matrix adhesion but increased cadherin‐based cell–cell interaction. Different from that in 2D culture, where MSCs exhibited branched and multiple‐directed F‐actin stress bundles at the cell edge and strengthened s...
Source: Journal of Cellular and Molecular Medicine - February 28, 2017 Category: Molecular Biology Authors: Ying Zhou, Haiyan Chen, Hong Li, Yaojiong Wu Tags: Original Article Source Type: research

Baicalin positively regulates osteoclast function by activating MAPK/Mitf signalling
In this study, we investigated the regulation of osteoclast differentiation by baicalin, which is a natural molecule extracted from Eucommiaulmoides (small tree native to China). It was determined that baicalin enhanced osteoclast maturation and bone resorption activity in a dose‐dependent manner. Moreover, this involves the activation of MAPK, increased Mitf nuclear translocation and up‐regulation of downstream osteoclast‐related target genes expression. The baicalin‐induced effect on osteoclast differentiation can be mimicked by specific inhibitors of p‐ERK (U0126) and the Mitf‐specific siRNA, respectively. P...
Source: Journal of Cellular and Molecular Medicine - February 2, 2017 Category: Molecular Biology Authors: Li Lu, Li Rao, Huanhuan Jia, Jun Chen, Xingyan Lu, Guozhu Yang, Qingnan Li, Kenneth Ka Ho Lee, Li Yang Tags: Original Article Source Type: research

Zinc rescues obesity ‐induced cardiac hypertrophy via stimulating metallothionein to suppress oxidative stress‐activated BCL10/CARD9/p38 MAPK pathway
In this study, we investigated the mechanisms by which zinc inactivates p38 MAPK to prevent ORCH. Mice (4‐week old) were fed either high fat diet (HFD, 60% kcal fat) or normal diet (ND, 10% kcal fat) containing variable amounts of zinc (deficiency, normal and supplement) for 3 and 6 months. P38 MAPK siRNA and the p38 MAPK inhibitor SB203580 were used to suppress p38 MAPK activity in vitro and in vivo, respectively. HFD activated p38 MAPK and increased expression of B‐cell lymphoma/CLL 10 (BCL10) and caspase recruitment domain family member 9 (CARD9). These responses were enhanced by zinc deficiency and attenuated by zi...
Source: Journal of Cellular and Molecular Medicine - February 2, 2017 Category: Molecular Biology Authors: Shudong Wang, Junlian Gu, Zheng Xu, Zhiguo Zhang, Tao Bai, Jianxiang Xu, Jun Cai, Gregory Barnes, Qiu ‐Ju Liu, Jonathan H. Freedman, Yonggang Wang, Quan Liu, Yang Zheng, Lu Cai Tags: Original Article Source Type: research

(Pro)renin receptor (ATP6AP2) depletion arrests As4.1 cells in the G0/G1 phase thereby increasing formation of primary cilia
Abstract The (pro)renin receptor [(P)RR, ATP6AP2] is a multifunctional transmembrane protein that activates local renin–angiotensin systems, but also interacts with Wnt pathways and vacuolar H+‐ATPase (V‐ATPase) during organogenesis. The aim of this study was to characterize the role of ATP6AP2 in the cell cycle in more detail. ATP6AP2 down‐regulation by siRNA in renal As4.1 cells resulted in a reduction in the rate of proliferation and a G0/G1 phase cell cycle arrest. We identified a number of novel target genes downstream of ATP6AP2 knock‐down that were related to the primary cilium (Bbs‐1, Bbs‐3, Bbs‐7, ...
Source: Journal of Cellular and Molecular Medicine - January 31, 2017 Category: Molecular Biology Authors: Heike Wanka, Philipp Lutze, Doreen Staar, Barbara Peters, Anica Morch, Lukas Vogel, Ravi Kumar Chilukoti, Georg Homuth, Jaroslaw Sczodrok, Inga B äumgen, Jörg Peters Tags: Original Article Source Type: research

Crosstalk between Smad2/3 and specific isoforms of ERK in TGF ‐β1‐induced TIMP‐3 expression in rat chondrocytes
This study investigated the roles of ERK1 and ERK2 in transforming growth factor‐β1 (TGF‐β1)‐induced tissue inhibitor of metalloproteinases‐3 (TIMP‐3) expression in rat chondrocytes, and the specific roles of ERK1 and ERK2 in crosstalk with Smad2/3 were investigated to demonstrate the molecular mechanism of ERK1/2 regulation of TGF‐β1 signalling. To examine the interaction of specific isoforms of ERK and the Smad2/3 signalling pathway, chondrocytes were infected with LV expressing either ERK1 or ERK2 siRNA and stimulated with or without TGF‐β1. At indicated time‐points, TIMP‐3 expression was determine...
Source: Journal of Cellular and Molecular Medicine - January 31, 2017 Category: Molecular Biology Authors: Yanhui Zhu, Jianhua Gu, Tong Zhu, Chen Jin, Xiaopeng Hu, Xiang Wang Tags: Original Article Source Type: research

FGF2 antagonizes aberrant TGF β regulation of tropomyosin: role for posterior capsule opacity
Abstract Transforming growth factor (TGF) β2 and fibroblast growth factor (FGF) 2 are involved in regulation of posterior capsule opacification (PCO) and other processes of epithelial–mesenchymal transition (EMT) such as cancer progression, wound healing and tissue fibrosis as well as normal embryonic development. We previously used an in vivo rodent PCO model to show the expression of tropomyosin (Tpm) 1/2 was aberrantly up‐regulated in remodelling the actin cytoskeleton during EMT. In this in vitro study, we show the Tpms family of cytoskeleton proteins are involved in regulating and stabilizing actin microfilaments...
Source: Journal of Cellular and Molecular Medicine - November 30, 2016 Category: Molecular Biology Authors: Eri Kubo, Shinsuke Shibata, Teppei Shibata, Etsuko Kiyokawa, Hiroshi Sasaki, Dhirendra P. Singh Tags: Original Article Source Type: research

CARD9 gene silencing with siRNA protects rats against severe acute pancreatitis: CARD9 ‐dependent NF‐κB and P38MAPKs pathway
In this study, small interfering RNA (siRNA) was used to reduce the levels of CARD9 expression in sodium taurocholate‐stimulated SAP rats. CARD9 was overexpressed in SAP rats, which correlated with the severity of pancreatitis. When compared to the untreated group, the cohort that received the siRNA treatment demonstrated a significant reduction in pancreatic injury, neutrophil infiltration, myeloperoxidase activity and pro‐inflammatory cytokines. Furthermore, siRNAs showed that the reduction of CARD9 in SAP rats down‐regulated the expression of NF‐κBp65 and P38MAPK which are involved in the transcription and rele...
Source: Journal of Cellular and Molecular Medicine - November 30, 2016 Category: Molecular Biology Authors: Zhi ‐wen Yang, Xiao‐xiao Meng, Chun Zhang, Ping Xu Tags: Original Article Source Type: research

Role of protein arginine methyltransferase 5 in inflammation and migration of fibroblast ‐like synoviocytes in rheumatoid arthritis
Abstract To probe the role of protein arginine methyltransferase 5 (PRMT5) in regulating inflammation, cell proliferation, migration and invasion of fibroblast‐like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA). FLSs were separated from synovial tissues (STs) from patients with RA and osteoarthritis (OA). An inhibitor of PRMT5 (EPZ015666) and short interference RNA (siRNA) against PRMT5 were used to inhibit PRMT5 expression. The standard of protein was measured by Western blot or immunofluorescence. The excretion and genetic expression of inflammatory factors were, respectively, estimated by enzyme‐l...
Source: Journal of Cellular and Molecular Medicine - October 31, 2016 Category: Molecular Biology Authors: Dongying Chen, Shan Zeng, Mingcheng Huang, Hanshi Xu, Liuqin Liang, Xiuyan Yang Tags: Original Article Source Type: research

Autophagy activated by tuberin/mTOR/p70S6K suppression is a protective mechanism against local anaesthetics neurotoxicity
Abstract The local anaesthetics (LAs) are widely used for peripheral nerve blocks, epidural anaesthesia, spinal anaesthesia and pain management. However, exposure to LAs for long duration or at high dosage can provoke potential neuronal damages. Autophagy is an intracellular bulk degradation process for proteins and organelles. However, both the effects of LAs on autophagy in neuronal cells and the effects of autophagy on LAs neurotoxicity are not clear. To answer these questions, both lipid LAs (procaine and tetracaine) and amide LAs (bupivacaine, lidocaine and ropivacaine) were administrated to human neuroblastoma SH‐S...
Source: Journal of Cellular and Molecular Medicine - October 31, 2016 Category: Molecular Biology Authors: Jingwei Xiong, Qiuyue Kong, Leyang Dai, He Ma, Xiaofei Cao, Li Liu, Zhengnian Ding Tags: Original Article Source Type: research

Enhanced pro ‐protein convertase subtilisin/kexin type 9 expression by C‐reactive protein through p38MAPK‐HNF1α pathway in HepG2 cells
Abstract Plasma C‐reactive protein (CRP) concentration is associated positively with cardiovascular risk, including dyslipidemia. We suggested a regulating role of CRP on pro‐protein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of low‐density lipoprotein (LDL) metabolism, and demonstrated the PCSK9 as a pathway linking CRP and LDL regulation. Firstly, experiments were carried out in the presence of human CRP on the protein and mRNA expression of PCSK9 and LDL receptor (LDLR) in human hepatoma cell line HepG2 cells. Treatment with CRP (10 μg/ml) enhanced significantly the mRNA and protein expression of...
Source: Journal of Cellular and Molecular Medicine - September 16, 2016 Category: Molecular Biology Authors: Chuan ‐Jue Cui, Sha Li, Cheng‐Gang Zhu, Jing Sun, Ying Du, Yan Zhang, Na‐Qiong Wu, Yuan‐Lin Guo, Rui‐Xia Xu, Ying Gao, Jian‐Jun Li Tags: Original Article Source Type: research

Hypoxanthine induces cholesterol accumulation and incites atherosclerosis in apolipoprotein E‐deficient mice and cells
In this study, we investigated the role of hypoxanthine on cholesterol synthesis and atherosclerosis development, particularly in apolipoprotein E (APOE)‐deficient mice. The effect of hypoxanthine on the regulation of cholesterol synthesis and atherosclerosis were evaluated in Apoe knockout (KO) mice and cultured HepG2 cells. Hypoxanthine markedly increased serum cholesterol levels and the atherosclerotic plaque area in Apoe KO mice. In HepG2 cells, hypoxanthine increased intracellular ROS production. Hypoxanthine increased cholesterol accumulation and decreased APOE and ATP‐binding cassette transporter A1 (ABCA1) mRNA...
Source: Journal of Cellular and Molecular Medicine - July 10, 2016 Category: Molecular Biology Authors: Hye‐Myung Ryu, You‐Jin Kim, Eun‐Joo Oh, Se‐Hyun Oh, Ji‐Young Choi, Jang‐Hee Cho, Chan‐Duck Kim, Sun‐Hee Park, Yong‐Lim Kim Tags: Original Article Source Type: research