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JNK AND Smad

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https://www.readbyqxmd.com/read/28919027/macrolactin-f-inhibits-rankl-mediated-osteoclastogenesis-by-suppressing-akt-mapk-and-nfatc1-pathways-and-promotes-osteoblastogenesis-through-a-bmp-2-smad-akt-runx2-signaling-pathway
#1
Liang Li, Mahesh Sapkota, Ming Gao, Hyukjae Choi, Yunjo Soh
The balance between bone formation and bone resorption is maintained by osteoblasts and osteoclasts. In the current study, macrolactin F (MF) was investigated for novel biological activity on the receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclastogenesis in primary bone marrow-derived macrophages (BMMs). We found that RANKL-induced osteoclast formation and differentiation from BMMs was significantly inhibited by MF in a dose-dependent manner without cytotoxicity. RANKL-induced F-actin ring formation and bone resorption activity in BMMs which was attenuated by MF...
September 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28874783/hyperactive-tgf-%C3%AE-signaling-in-smooth-muscle-cells-exposed-to-hiv-protein-s-and-cocaine-role-in-pulmonary-vasculopathy
#2
Pranjali Dalvi, Himanshu Sharma, Tomara Konstantinova, Miles Sanderson, Amy O' Brien-Ladner, Navneet K Dhillon
We earlier demonstrated synergistic increase in the proliferation of pulmonary smooth muscle cells on exposure to HIV-proteins and/or cocaine due to severe down-modulation of bone morphogenetic protein receptor (BMPR) axis: the anti-proliferative arm of TGF-β super family of receptors. Here, now we demonstrate the effect of HIV-Tat and cocaine on the proliferative TGF-β signaling cascade. We observed a significant increase in the secretion of TGF-β1 ligand along with enhanced protein expression of TGFβ Receptor (TGFβR)-1, TGFβR-2 and phosphorylated SMAD2/3 in human pulmonary arterial smooth muscle cells on treatment with cocaine and Tat...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28873461/interleukin-17-induces-human-alveolar-epithelial-to-mesenchymal-cell-transition-via-the-tgf-%C3%AE-1-mediated-smad2-3-and-erk1-2-activation
#3
Ting Wang, Yuan Liu, Jing-Feng Zou, Zhen-Shun Cheng
Idiopathic pulmonary fibrosis (IPF) is a chronic and usually progressive lung disease and the epithelial-mesenchymal transition (EMT) may play an important role in the pathogenesis of pulmonary fibrosis. IL-17 is a proinflammatory cytokine which promotes EMT profiles in lung inflammatory diseases. In this study, we investigated the effect of IL-17 on EMT in alveolar epithelial cell line A549 and the role of TGFβ1-Smad and ERK signaling pathways in the process. Morphological observation on the cells was performed under inverted microscope...
2017: PloS One
https://www.readbyqxmd.com/read/28858391/pterocarpus-santalinus-l-regulated-ultraviolet-b-irradiation-induced-procollagen-reduction-and-matrix-metalloproteinases-expression-through-activation-of-tgf-%C3%AE-smad-and-inhibition-of-the-mapk-ap-1-pathway-in-normal-human-dermal-fibroblasts
#4
Wei Gao, Pei Lin, Eunson Hwang, Yushuai Wang, Zhengfei Yan, Hien T T Ngo, Tae-Hoo Yi
Ultraviolet light-induced reactive oxygen species (ROS) damage human skin and prematurely cause aging. A growing body of research is focusing on considering plants and plant-derived compounds as anti-photoaging therapeutic material. Pterocarpus santalinus L., as an Indian traditional medicine, possesses antidiabetic, anti-inflammatory and antioxidative effects. Here, we studied the anti-photoaging effects of ethanolic extract of P. santalinus L. heartwood (EPS) on ultraviolet radiation B (UVB)-irradiated normal human dermal fibroblasts (NHDFs)...
August 31, 2017: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/28820432/rho-kinase-blockade-attenuates-podocyte-apoptosis-by-inhibiting-the-notch-signaling-pathway-in-diabetic-nephropathy
#5
Keiichiro Matoba, Daiji Kawanami, Yosuke Nagai, Yusuke Takeda, Tomoyo Akamine, Sho Ishizawa, Yasushi Kanazawa, Tamotsu Yokota, Kazunori Utsunomiya
Podocyte apoptosis is a key process in the onset of diabetic nephropathy. A significant body of evidence shows that the Notch signaling pathway plays a central role in this process. We found that Rho-kinase mediates transforming growth factor β (TGF-β)-induced Notch ligand Jag1 expression. Importantly, TGF-β-mediated podocyte apoptosis was attenuated by Rho-kinase inhibition. Mechanistically, Rho-kinase regulated Jag1 induction via the extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) but not Smad pathways...
August 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28689803/lipopolysaccharides-induce-smad2-phosphorylation-through-pi3k-akt-and-mapk-cascades-in-hsc-t6-hepatic-stellate-cells
#6
Ying-Hsien Kao, Po-Han Chen, Tin-Ya Wu, Yu-Chun Lin, Ming-Shian Tsai, Po-Huang Lee, Tzong-Shyuan Tai, Huoy-Rou Chang, Cheuk-Kwan Sun
AIMS: Endotoxemia and its pro-fibrogenic signaling play a significant role in the development of hepatic fibrosis. This study investigated whether lipopolysaccharide (LPS) directly activate cultured HSC-T6 hepatic stellate cells (HSCs) through triggering Smad-dependent pro-fibrogenic signaling pathway. MAIN METHODS: Direct cell counting and assays for cell proliferation and migration were used to measure the effects of LPS on HSC behaviors. Quantitative PCR, Western blot, and gelatin zymography were used to quantify the molecular effects of LPS on expression of HSC activation markers and signaling activity...
September 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/28624424/fusaric-acid-fa-protects-heart-failure-induced-by-isoproterenol-isp-in-mice-through-fibrosis-prevention-via-tgf-%C3%AE-1-smads-and-pi3k-akt-signaling-pathways
#7
Xin Li, Zhou-Long Zhang, Hui-Fen Wang
Fusaric acid (FA) is a novel compound derived from a class of nicotinic acid derivatives, exhibiting activity against cancers. However, its role in regulating cardiac injury is limited. Our study was aimed to investigate the role and the underlying molecular mechanism of FA in heart fibrosis and hypertrophy. Isoproterenol (ISP) was used to induce cardiac fibrosis and hypertrophy in vitro and in vivo. FA administration ameliorated hypertrophy by reducing atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β -myosin heavy chain (β-MHC) in vitro and in vivo...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28621502/amniotic-membrane-stimulates-cell-migration-by-modulating-transforming-growth-factor-%C3%AE-signaling
#8
Catalina Ruiz-Cañada, Ángel Bernabé-García, Sergio Liarte, Carmen Luisa Insausti, Diego Angosto, José María Moraleda, Gregorio Castellanos, Francisco José Nicolás
Keratinocyte migration is a mandatory aspect of wound-healing. We have previously shown that Amniotic Membrane (AM) applied to chronic wounds assists healing through a process resulting in overexpression of c-Jun at the wound's leading edge. Also, we have demonstrated that amniotic membrane modifies the genetic program induced by TGF-ß in chronic wounds. In this paper, we used a scratch assay of Mv1Lu and HaCaT cells to examine the influence of AM application on the underlying signaling during scratch closure...
June 16, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28568893/tgf-%C3%AE-signaling-directly-regulates-transcription-and-functional-expression-of-the-electrogenic-sodium-bicarbonate-cotransporter-1-nbce1-slc4a4-via-smad4-in-mouse-astrocytes
#9
Shokoufeh Khakipoor, Christian Ophoven, Magdalena Schrödl-Häußel, Melanie Feuerstein, Bernd Heimrich, Joachim W Deitmer, Eleni Roussa
The electrogenic sodium bicarbonate cotransporter NBCe1 (SLC4A4) expressed in astrocytes regulates intracellular and extracellular pH. Here, we introduce transforming growth factor beta (TGF-β) as a novel regulator of NBCe1 transcription and functional expression. Using hippocampal slices and primary hippocampal and cortical astrocyte cultures, we investigated regulation of NBCe1 and elucidated the underlying signaling pathways by RT-PCR, immunoblotting, immunofluorescence, intracellular H((+) ) recording using the H((+) ) -sensitive dye 2',7'-bis-(carboxyethyl)-5-(and-6)-carboxyfluorescein, mink lung epithelial cell (MLEC) assay, and chromatin immunoprecipitation...
August 2017: Glia
https://www.readbyqxmd.com/read/28478809/aloesin-from-aloe-vera-accelerates-skin-wound-healing-by-modulating-mapk-rho-and-smad-signaling-pathways-in-vitro-and-in-vivo
#10
Hussain Mustatab Wahedi, Minsun Jeong, Jae Kyoung Chae, Seon Gil Do, Hyeokjun Yoon, Sun Yeou Kim
BACKGROUND: Cutaneous wound healing is a complex process involving various regulatory factors at the molecular level. Aloe vera is widely used for cell rejuvenation, wound healing, and skin moisturizing. HYPOTHESIS/PURPOSE: This study aimed to investigate the effects of aloesin from Aloe vera on cutaneous wound healing and mechanisms involved therein. STUDY DESIGN: This study consisted of both in vitro and in vivo experiments involving skin cell lines and mouse model to demonstrate the wound healing effects of aloesin by taking into account several parameters ranging from cultured cell migration to wound healing in mice...
May 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28406452/suppression-of-hepatic-epithelial-to-mesenchymal-transition-by-melittin-via-blocking-of-tgf%C3%AE-smad-and-mapk-jnk-signaling-pathways
#11
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
https://www.readbyqxmd.com/read/28241317/tgf%C3%AE-2-induces-the-formation-of-cross-linked-actin-networks-clans-in-human-trabecular-meshwork-cells-through-the-smad-and-non-smad-dependent-pathways
#12
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
https://www.readbyqxmd.com/read/28142299/tgf-%C3%AE-1-protects-intestinal-integrity-and-influences-smads-and-mapk-signal-pathways-in-ipec-j2-after-tnf-%C3%AE-challenge
#13
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...
April 2017: Innate Immunity
https://www.readbyqxmd.com/read/28092676/intracellular-il-37b-interacts-with-smad3-to-suppress-multiple-signaling-pathways-and-the-metastatic-phenotype-of-tumor-cells
#14
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...
May 18, 2017: Oncogene
https://www.readbyqxmd.com/read/27783979/a-requirement-for-zak-kinase-activity-in-canonical-tgf-%C3%AE-signaling
#15
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
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
#16
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
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
#17
Long-Xing Xue, Zhong-Hang Xu, Jiao-Qi Wang, Yang Cui, 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...
November 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
#18
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
#19
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
#20
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
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