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JNK AND Smad

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https://www.readbyqxmd.com/read/27783979/a-requirement-for-zak-kinase-activity-in-canonical-tgf-%C3%AE-signaling
#1
Shyam Nyati, Areeb Chator, Katerina Schinske, Brandon S Gregg, Brian Dale Ross, Alnawaz Rehemtulla
The sterile alpha motif and leucine zipper containing kinase ZAK (AZK, MLT, MLK7), is a MAPK-kinase kinase (MKKK). Like most MAPKKKs which are known to activate the c-Jun. amino-terminal kinase (JNK) pathway, ZAK has been shown to participate in the transduction of Transforming growth factor-β (TGF-β)-mediated non-canonical signaling. A role for ZAK in SMAD-dependent, canonical TGF-β signaling has not been previously appreciated. Using a combination of functional genomics and biochemical techniques, we demonstrate that ZAK regulates canonical TGFβRI/II signaling in lung and breast cancer cell lines and may serve as a key node in the regulation of TGFBR kinase activity...
October 23, 2016: Translational Oncology
https://www.readbyqxmd.com/read/27770286/dietary-oxidized-tyrosine-o-tyr-stimulates-tgf-%C3%AE-1-induced-extracellular-matrix-production-via-the-jnk-p38-signaling-pathway-in-rat-kidneys
#2
Zhuqing Leslie Li, Yonghui Shi, Yinyi Ding, Yumei Ran, Guowei Le
Oxidized tyrosine (O-Tyr) products have been detected in commercial food and have been demonstrated to induce liver injury in our previous study, but the precise mechanisms of the impact induced by dietary O-Tyr are still unclear. Kidney plays an important role in the metabolism of protein. Accumulation of O-Tyr products, especially the dityrosine (Dityr) and advanced oxidation protein products (AOPPs), in vivo was shown to be associated with many kidney diseases. Therefore, this study determined whether chronic exposure to dietary O-Tyr impaired renal function in rats...
October 21, 2016: Amino Acids
https://www.readbyqxmd.com/read/27769861/activin-a-smads-signaling-pathway-negatively-regulates-oxygen-glucose-deprivation-induced-autophagy-via-suppression-of-jnk-and-p38-mapk-pathways-in-neuronal-pc12-cells
#3
Long-Xing Xue, Zhong-Hang Xu, Jiao-Qi Wang, Cui Yang, Hong-Yu Liu, Wen-Zhao Liang, Qiu-Ye Ji, Jin-Ting He, Yan-Kun Shao, Jing Mang, Zhong-Xin Xu
Activin A (Act A), a member of the transforming growth factor-beta (TGF-β), reduces neuronal apoptosis during cerebral ischemia through Act A/Smads signaling pathway. However, little is known about the effect of Act A/Smads pathway on autophagy in neurons. Here, we found that oxygen-glucose deprivation (OGD)-induced autophagy was suppressed by exogenous Act A in a concentration-dependent manner and enhanced by Act A/Smads pathway inhibitor (ActRIIA-Ab) in neuronal PC12 cells. These results indicate that Act A/Smads pathway negatively regulates autophagy in OGD-treated PC12 cells...
October 18, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27703224/gallic-acid-prevents-isoproterenol-induced-cardiac-hypertrophy-and-fibrosis-through-regulation-of-jnk2-signaling-and-smad3-binding-activity
#4
Yuhee Ryu, Li Jin, Hae Jin Kee, Zhe Hao Piao, Jae Yeong Cho, Gwi Ran Kim, Sin Young Choi, Ming Quan Lin, Myung Ho Jeong
Gallic acid, a type of phenolic acid, has been shown to have beneficial effects in inflammation, vascular calcification, and metabolic diseases. The present study was aimed at determining the effect and regulatory mechanism of gallic acid in cardiac hypertrophy and fibrosis. Cardiac hypertrophy was induced by isoproterenol (ISP) in mice and primary neonatal cardiomyocytes. Gallic acid pretreatment attenuated concentric cardiac hypertrophy. It downregulated the expression of atrial natriuretic peptide, brain natriuretic peptide, and beta-myosin heavy chain in vivo and in vitro...
October 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27649211/dioxinodehydroeckol-enhances-the-differentiation-of-osteoblasts-by-regulating-the-expression-of-phospho-smad1-5-8
#5
Byul-Nim Ahn, Fatih Karadeniz, Chang-Suk Kong, Ki-Ho Nam, Mi-Soon Jang, Youngwan Seo, Han Seong Kim
Lack of bone formation-related health problems are a major problem for the aging population in the modern world. As a part of the ongoing trend of developing natural substances that attenuate osteoporotic bone loss conditions, dioxinodehydroeckol (DHE) from edible brown alga Ecklonia cava was tested for its effects on osteoblastogenic differentiation in MC3T3-E1 pre-osteoblasts. DHE was observed to successfully enhance osteoblast differentiation, as indicated by elevated cell proliferation, alkaline phosphatase activity, intracellular cell mineralization, along with raised levels of osteoblastogenesis indicators at the concentration of 20 μM...
September 14, 2016: Marine Drugs
https://www.readbyqxmd.com/read/27617577/rn1-a-novel-galectin-3-inhibitor-inhibits-pancreatic-cancer-cell-growth-in-vitro-and-in-vivo-via-blocking-galectin-3-associated-signaling-pathways
#6
L Zhang, P Wang, Y Qin, Q Cong, C Shao, Z Du, X Ni, P Li, K Ding
Galectin-3 (Gal-3) has been implicated in pancreatic ductal adenocarcinoma (PDAC), and its candidacy as a therapeutic target has been evaluated. Gal-3 is widely upregulated in tumors, and its expression is associated with the development and malignancy of PDAC. In the present study, we demonstrate that a polysaccharide, RN1, purified from the flower of Panax notoginseng binds to Gal-3 and suppresses its expression. In addition, RN1 markedly inhibits PDAC cells growth in vitro, in vivo and in patient-derived xenografts...
September 12, 2016: Oncogene
https://www.readbyqxmd.com/read/27573189/collagen-regulates-transforming-growth-factor-%C3%AE-receptors-of-hl-1-cardiomyocytes-through-activation-of-stretch-and-integrin-signaling
#7
Yen-Yu Lu, Yung-Kuo Lin, Yu-Hsun Kao, Cheng-Chih Chung, Yung-Hsin Yeh, Shih-Ann Chen, Yi-Jen Chen
The extracellular matrix (ECM) and transforming growth factor-β (TGF)-β are important in cardiac fibrosis, however, the effects of the ECM on TGF‑β signaling remain to be fully elucidated. The aims of the present study were to evaluate the role of collagen in TGF‑β signaling and examine the underlying mechanisms. In the present study, western blot analysis was used to examine TGF‑β signaling in HL‑1 cells treated with and without (control) type I collagen (10 µg/ml), which was co‑administered with either an anti‑β1 integrin antibody (10 µg/ml) or a stretch‑activated channel inhibitor (gadolinium; 50 µM)...
October 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27519288/hexachlorobenzene-modulates-the-crosstalk-between-the-aryl-hydrocarbon-receptor-and-transforming-growth-factor-%C3%AE-1-signaling-enhancing-human-breast-cancer-cell-migration-and-invasion
#8
Noelia Miret, Carolina Pontillo, Clara Ventura, Alejandro Carozzo, Florencia Chiappini, Diana Kleiman de Pisarev, Natalia Fernández, Claudia Cocca, Andrea Randi
Given the number of women affected by breast cancer, considerable interest has been raised in understanding the relationships between environmental chemicals and disease onset. Hexachlorobenzene (HCB) is a dioxin-like compound that is widely distributed in the environment and is a weak ligand of the aryl hydrocarbon receptor (AhR). We previously demonstrated that HCB acts as an endocrine disruptor capable of stimulating cell proliferation, migration, invasion, and metastasis in different breast cancer models...
July 29, 2016: Toxicology
https://www.readbyqxmd.com/read/27406972/an-investigation-of-bmp-7-mediated-alterations-to-bmp-signalling-components-in-human-tenocyte-like-cells
#9
Franka Klatte-Schulz, Gerry Giese, Christopher Differ, Susann Minkwitz, Karen Ruschke, Regina Puts, Petra Knaus, Britt Wildemann
The incidence of tendon re-tears post-surgery is an ever present complication. It is suggested that the application of biological factors, such as bone morphogenetic protein 7 (BMP-7), can reduce complication rates by promoting tenogenic characteristics in in vitro studies. However, there remains a dearth of information in regards to the mechanisms of BMP-7 signalling in tenocytes. Using primary human tenocyte-like cells (hTLCs) from the supraspinatus tendon the BMP-7 signalling pathway was investigated: induction of the BMP associated Smad pathway and non-Smad pathways (AKT, p38, ERK1/2 and JNK); alterations in gene expression of BMP-7 associated receptors, Smad pathway components, Smad target gene (ID1) and tenogenic marker scleraxis...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27392951/role-of-c-jun-n-terminal-kinase-in-hepatocellular-carcinoma-development
#10
Juan Wang, Guixiang Tai
Hepatocellular carcinoma (HCC) is among the most frequently occurring cancers and the leading causes of cancer mortality worldwide. Identification of the signaling pathways regulating liver carcinogenesis is critical for developing novel chemoprevention and targeted therapies. C-Jun N-terminal kinase (JNK) is a member of a larger group of serine/threonine (Ser/Thr) protein kinases known as the mitogen-activated protein kinase (MAPK) family. JNK is an important signaling component that converts external stimuli into a wide range of cellular responses, including cell proliferation, differentiation, survival, migration, invasion, and apoptosis, as well as the development of inflammation, fibrosis, cancer growth, and metabolic diseases...
July 8, 2016: Targeted Oncology
https://www.readbyqxmd.com/read/27347335/adenosine-promotes-foxp3-expression-in-treg-cells-in-sepsis-model-by-activating-jnk-ap-1-pathway
#11
Rui Bao, Jiong Hou, Yan Li, Jinjun Bian, Xiaoming Deng, Xiaoyan Zhu, Tao Yang
OBJECTIVES: Forkhead/winged helix transcription factor p3 (Foxp3) increases in CD4(+)CD25(+)Treg cells during sepsis; however, related mechanisms are unclear. Our study aimed to explore the possible molecular mechanisms of high expression of Foxp3 in Treg cells during sepsis. METHODS: Sepsis was induced by cecal ligation and puncture (CLP) method. CD4(+)CD25(+)Treg cells were isolated from peripheral blood and identified by flow cytometry (FCM). Treg cells were cultured with or without adenosine, adenosine agonist, adenosine antagonist, SMAD family member 3 (Smad3) agonist (transforming growth factor (TGF)-β1), or C-Jun N-Terminal Kinase (JNK) inhibitor...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27133302/paeoniflorin-suppresses-tgf-%C3%AE-mediated-epithelial-mesenchymal-transition-in-pulmonary-fibrosis-through-a-smad-dependent-pathway
#12
Yu Ji, Yan-Nong Dou, Qian-Wen Zhao, Ji-Zhou Zhang, Yan Yang, Ting Wang, Yu-Feng Xia, Yue Dai, Zhi-Feng Wei
AIM: Paeoniflorin has shown to attenuate bleomycin-induced pulmonary fibrosis (PF) in mice. Because the epithelial-mesenchymal transition (EMT) in type 2 lung endothelial cells contributes to excessive fibroblasts and myofibroblasts during multiple fibrosis of tissues, we investigated the effects of paeoniflorin on TGF-β mediated pulmonary EMT in bleomycin-induced PF mice. METHODS: PF was induced in mice by intratracheal instillation of bleomycin (5 mg/kg). The mice were orally treated with paeoniflorin or prednisone for 21 d...
June 2016: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/27123137/smad4-inhibits-cell-migration-via-suppression-of-jnk-activity-in-human-pancreatic-carcinoma-panc-1-cells
#13
Xueying Zhang, Junxia Cao, Yujun Pei, Jiyan Zhang, Qingyang Wang
Smad4 is a common Smad and is a key downstream regulator of the transforming growth factor-β signaling pathway, in which Smad4 often acts as a potent tumor suppressor and functions in a highly context-dependent manner, particularly in pancreatic cancer. However, little is known regarding whether Smad4 regulates other signaling pathways involved in pancreatic cancer. The present study demonstrated that Smad4 downregulates c-Jun N-terminal kinase (JNK) activity using a Smad4 loss-of-function or gain-of-function analysis...
May 2016: Oncology Letters
https://www.readbyqxmd.com/read/26971374/tcdd-promoted-emt-of-hfpecs-via-ahr-which-involved-the-activation-of-egfr-erk-signaling
#14
Zhan Gao, Yongjun Bu, Xiaozhuan Liu, Xugang Wang, Guofu Zhang, Erhui Wang, Shibin Ding, Yongfeng Liu, Ruling Shi, Qiaoyun Li, Jianhong Fu, Zengli Yu
One critical step of second palatal fusion is the newly formed medial epithelia seam (MES) disintegration, which involves apoptosis, epithelial to mesenchymal transition (EMT), and cell migration. Although the environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) produces cleft palate at high rates, little is known about the effects of TCDD exposure on the fate of palatal epithelial cells. By using primary epithelial cells isolated from human fetal palatal shelves (hFPECs), we show that TCDD increased cell proliferation and EMT, as demonstrated by increased the epithelial markers (E-cadherin and cytokeratin14) and enhanced the mesenchymal markers (vimentin and fibronectin), but had no effect on cell migration and apoptosis...
May 1, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/26950456/effects-of-c-jun-n-terminal-kinase-on-activin-a-smads-signaling-in-pc12-cell-suffered-from-oxygen-glucose-deprivation
#15
J Q Wang, Z H Xu, W Z Liang, J T He, Y Cui, H Y Liu, L X Xue, W Shi, Y K Shao, J Mang, Z X Xu
Activin A (Act A), a member of transforming growth factor-β (TGF-β) superfamily, is an early gene in response to cerebral ischemia. Growing evidences confirm the neuroprotective effect of Act A in ischemic injury through Act A/Smads signal activation. In this process, regulation networks are involved in modulating the outcomes of Smads signaling. Among these regulators, crosstalk between c-Jun N-terminal kinase (JNK) and Smads signaling has been found in the TGF-β induced epithelial-mesenchymal transition...
2016: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/26919250/gdf11-bmp11-activates-both-smad1-5-8-and-smad2-3-signals-but-shows-no-significant-effect-on-proliferation-and-migration-of-human-umbilical-vein-endothelial-cells
#16
Yong-Hui Zhang, Feng Cheng, Xue-Ting Du, Jin-Lai Gao, Xiao-Lin Xiao, Na Li, Shan-Liang Li, De Li Dong
GDF11/BMP11, a member of TGF-β superfamily, was reported to rejuvenate heart, skeletal muscle and blood vessel architecture in aged mice. However, the rejuvenative effects of GDF11 were questioned recently. Here, we investigated the effects of GDF11 on smad and non-smad signals in human umbilical vein endothelial cells (HUVECs) and the effects of GDF11 on proliferation and migration of HUVECs and primary rat aortic endothelial cells (RAECs). GDF11 factor purchased from two different companies (PeproTech and R&D Systems) was comparatively studied...
March 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/26912223/epithelial-microvesicles-promote-an-inflammatory-phenotype-in-fibroblasts
#17
J Bi, L Koivisto, G Owen, P Huang, Z Wang, Y Shen, L Bi, A Rokka, M Haapasalo, J Heino, L Häkkinen, H S Larjava
Microvesicles (MVs) are extracellular vesicles secreted by various cell types that are involved in intercellular communication. We hypothesized that in human periodontal disease, the pocket epithelium releases MVs, which then modulate gene expression in the underlying fibroblasts to control periodontal inflammation. MVs were isolated from culture medium of gingival epithelial cells (GECs) treated with oral bacterial biofilm extract or left untreated. Biofilm treatment significantly increased MV release from the GECs...
June 2016: Journal of Dental Research
https://www.readbyqxmd.com/read/26898453/transforming-growth-beta-1-contributes-to-isoflurane-postconditioning-against-cerebral-ischemia-reperfusion-injury-by-regulating-the-c-jun-n-terminal-kinase-signaling-pathway
#18
Sheng Wang, Jiangwen Yin, Mingyue Ge, Zhigang Dai, Yan Li, Junqiang Si, Ketao Ma, Li Li, Shanglong Yao
AIM: Cerebral ischemia-reperfusion (I/R) injury is a devastating complication in the perioperative period. Transforming growth factor beta (TGF-β) is a key protein that can participate in the repair and control process responses after I/R injury. Isoflurane is widely used in neurosurgery. Previous studies have shown that isoflurane preconditioning plays an important role in neuroprotection. However, the effects of isoflurane postconditioning on cerebral I/R injury have not yet been elucidated...
March 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/26889259/inhibitory-effect-of-bone-morphogenetic-protein-2-on-the-proliferation-of-giant-cell-tumor-of-bone-stromal-cells-in-vitro
#19
Baohua He, Guanping He, Xiaofei Zheng, Lihua Li, Mei Li, Hong Xia
The inhibitory effect of bone morphogenetic protein-2 (BMP-2) on the proliferation of giant cell tumor of bone stromal cells (GCTSCs) has not been fully elucidated. Therefore, the aim of this study was to evaluate the role of recombinant human BMP-2 (rhBMP-2) in the growth of GCTSCs. The effects of exposure to different concentrations of rhBMP-2 (0, 10, 100 and 300 ng/ml) for 1, 3, 5 and 7 days on GCTSC proliferation were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, the effect of treatment with rhBMP-2 (0 or 10 ng/ml) for 48 h on the cell cycle pattern of GCTSCs was examined by flow cytometry...
January 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/26879145/recombinant-human-bone-morphogenetic-protein-9-potently-induces-osteogenic-differentiation-of-human-periodontal-ligament-fibroblasts
#20
Sawako Fuchigami, Toshiaki Nakamura, Kirara Furue, Kotaro Sena, Yukiya Shinohara, Kazuyuki Noguchi
To accomplish effective periodontal regeneration for periodontal defects, several regenerative methods using growth and differentiation factors, including bone morphogenetic proteins (BMPs), have been developed. Bone morphogenetic protein-9 exhibits the most potent osteogenic activity of this growth factor family. However, it is unclear whether exogenous BMP-9 can induce osteogenic differentiation in human periodontal ligament (PDL) fibroblasts. Here, we examined the effects of recombinant human (rh) BMP-9 on osteoblastic differentiation in human PDL fibroblasts in vitro, compared with rhBMP-2...
April 2016: European Journal of Oral Sciences
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