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Ji-Hyun Park, Byoungduck Park, Kwan-Kyu Park
Transforming growth factor (TGF)-β1 plays a crucial role in the epithelial-to-mesenchymal transition (EMT) in hepatocytes and hepatic stellate cells (HSC), which contributes to the pathogenesis of liver fibrosis. Melittin (MEL) is a major component of bee venom and is effective in rheumatoid arthritis, pain relief, cancer cell proliferation, fibrosis and immune modulating activity. In this study, we found that MEL inhibits hepatic EMT in vitro and in vivo, regulating the TGFβ/Smad and TGFβ/nonSmad signaling pathways...
April 13, 2017: Toxins
Michela Montecchi-Palmer, Jaclyn Y Bermudez, Hannah C Webber, Gaurang C Patel, Abbot F Clark, Weiming Mao
Purpose: Increased intraocular pressure results from increased aqueous humor (AH) outflow resistance at the trabecular meshwork (TM) due to pathologic changes including the formation of cross-linked actin networks (CLANs). Transforming growth factor β2 (TGFβ2) is elevated in the AH and TM of primary open angle glaucoma (POAG) patients and induces POAG-associated TM changes, including CLANs. We determined the role of individual TGFβ2 signaling pathways in CLAN formation. Methods: Cultured nonglaucomatous human TM (NTM) cells were treated with control or TGFβ2, with or without the inhibitors of TGFβ receptor, Smad3, c-Jun N-terminal kinases (JNK), extracellular signal regulated kinase (ERK), P38, or Rho-associated protein kinase (ROCK)...
February 1, 2017: Investigative Ophthalmology & Visual Science
Kan Xiao, Shuting Cao, Lefei Jiao, Zehe Song, Jianjun Lu, Caihong Hu
The aim of this study was to investigate the protective effects of TGF-β1 on intestinal epithelial barrier, as well as canonical Smad and MAPK signal pathways involved in these protection processes by a IPEC-J2 model stimulated with TNF-α. IPEC-J2 monolayers were treated without or with TNF-α in the absence or presence of TGF-β1. The results showed that TGF-β1 pretreatment ameliorated TNF-α-induced intestinal epithelial barrier disturbances as indicated by decrease of transepithelial electrical resistance (TER) and increase of paracellular permeability...
January 1, 2017: Innate Immunity
C Luo, Y Shu, J Luo, D Liu, D-S Huang, Y Han, C Chen, Y-C Li, J-M Zou, J Qin, Y Wang, D Li, S-S Wang, G-M Zhang, J Chen, Z-H Feng
Multiple signaling pathways that promote tumor cell metastasis are differentially activated in low/non-metastatic and metastatic tumor cells, resulting in the differential expression of metastasis-related genes. The underlying mechanism may involve the alterations of the intrinsic negative regulation in tumor cells. Here we report that the differential expression of interleukin-37b (IL-37b) in tumor cells alters the intrinsic negative regulation of signaling pathways, resulting in the difference of metastatic capacity...
January 16, 2017: Oncogene
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...
December 2016: Translational Oncology
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...
February 2017: Amino Acids
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
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
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
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
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
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
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
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...
December 2016: Targeted Oncology
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
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
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
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
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...
February 29, 2016: Cellular and Molecular Biology
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
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