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Smad3 AND Beta cells

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https://www.readbyqxmd.com/read/28637791/store-operated-calcium-entry-suppressed-tgf%C3%AE-1-smad3-signaling-pathway-in-glomerular-mesangial-cells
#1
Sarika Chaudhari, Weizu Li, Yanxia Wang, Hui Jiang, Yuhong Ma, Mark E Davis, Jonathan E Zuckerman, Rong Ma
Our previous study demonstrated that the abundance of extracellular matrix proteins was suppressed by store-operated Ca2+ entry in mesangial cells (MCs). The present study was conducted to investigate the underlying mechanism focused on the transforming growth factor beta 1 (TGFβ1) - Smad3 pathway, a critical pathway for ECM expansion in diabetic kidneys. We hypothesized that SOCE suppressed ECM protein expression by inhibiting this pathway in MCs. In cultured human MCs, we observed that TGFβ1 (5 ng/ml for 15 hours) significantly increased Smad3 phosphorylation as evaluated by immunoblot...
June 21, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28608941/tgf-%C3%AE-stimulates-expression-of-chondroitin-polymerizing-factor-in-nucleus-pulposus-cells-through-the-smad3-rhoa-rock1-and-mapk-signaling-pathways
#2
Bo Hu, Chen Xu, Peng Cao, Ye Tian, Ying Zhang, Changgui Shi, Jun Xu, Wen Yuan, Huajiang Chen
The enzyme chondroitin polymerizing factor (ChPF) is primarily involved in extension of the chondroitin sulfate backbone required for the synthesis of sulfated glycosaminoglycan (sGAG). Transforming growth factor beta (TGF-β) upregulates sGAG synthesis in nucleus pulposus cells; however, the mechanisms mediating this induction are incompletely understood. Our study demonstrated that ChPF expression was negatively correlated with the grade of degenerative intervertebral disc disease. Treatment of nucleus pulposus cells with TGF-β induced ChPF expression and enhanced Smad2/3, RhoA/ ROCK activation, and the JNK, p38 and ERK1/2 MAPK signaling pathways...
June 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28518142/mir-130a-3p-attenuates-activation-and-induces-apoptosis-of-hepatic-stellate-cells-in-nonalcoholic-fibrosing-steatohepatitis-by-directly-targeting-tgfbr1-and-tgfbr2
#3
Yang Wang, Jinghua Du, Xuemin Niu, Na Fu, Rongqi Wang, Yuguo Zhang, Suxian Zhao, Dianxing Sun, Yuemin Nan
Nonalcoholic fibrosing steatohepatitis is a uniform process that occurs throughout nonalcoholic fatty liver disease (NAFLD). MicroRNAs (miRNAs) have been shown to be involved in the biological processes, but the role and molecular mechanism of miRNAs in NAFLD are not entirely clear. In this study, we observed a significant reduction in the expression of miR-130a-3p in livers of a mouse model with fibrosis induced by a methionine-choline-deficient diet, of NAFLD patients, and in activated hepatic stellate cells (HSCs)...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28515224/activin-a-regulates-activation-of-mouse-neutrophils-by-smad3-signalling
#4
Yan Qi, Jingyan Ge, Chunhui Ma, Na Wu, Xueling Cui, Zhonghui Liu
Activin A, a member of the transforming growth factor beta superfamily, acts as a pro-inflammatory factor in acute phase response, and influences the pathological progress of neutrophil-mediated disease. However, whether activin A can exert an effect on the activities of neutrophils remains unclear. In this study, we found that the release of activin A was enhanced from neutrophils of mouse when stimulated with lipopolysaccharide. Furthermore, neutrophils were not only the source of activin A but also the target cells in response to activin A, in which canonical activin signalling components existed, and levels of ACTRIIA, SMAD3 and p-SMAD3 proteins were elevated in activin A-treated neutrophils...
May 2017: Open Biology
https://www.readbyqxmd.com/read/28433746/transforming-growth-factor-beta-1-signaling-regulates-neuroinflammation-and-apoptosis-in-mild-traumatic-brain-injury
#5
Rachel K Patel, Nithisha Prasad, Ram Kuwar, Debanjan Haldar, P M Abdul-Muneer
Mild traumatic brain injury (mTBI) is a low-level injury, which often remains undiagnosed, and in most cases it leads to death and disability as it advances as secondary injury. Therefore, it is important to study the underlying signaling mechanisms of mTBI-associated neurological ailments. While transforming growth factor-beta1 (TGF-β1) has a significant role in inflammation and apoptosis in myriads of other pathophysiological conditions, the precise function of increased TGF-β1 after mTBI is unknown. In this study, our objective is to study the physiological relevance and associated mechanisms of TGF-β1-mediated inflammation and apoptosis in mTBI...
April 19, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28424263/the-kielin-chordin-like-protein-kcp-attenuates-high-fat-diet-induced-obesity-and-metabolic-syndrome-in-mice
#6
Abdul Soofi, Katherine I Wolf, Margo P Emont, Nathan Qi, Gabriel Martinez-Santibanez, Edward Grimley, Wesam Ostwani, Gregory R Dressler
Obesity and its associated complications such as insulin resistance and non-alcoholic fatty liver disease are reaching epidemic proportions. In mice, the TGF-β superfamily is implicated in the regulation of white and brown adipose tissue differentiation. The kielin/chordin-like protein (KCP) is a secreted regulator of the TGF-β superfamily pathways that can inhibit both TGF-β and activin signals while enhancing bone morphogenetic protein (BMP) signaling. However, KCP's effects on metabolism and obesity have not been studied in animal models...
June 2, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28390311/metformin-mitigates-carbon-tetrachloride-induced-tgf-%C3%AE-1-smad3-signaling-and-liver-fibrosis-in-mice
#7
Kerui Fan, Kejia Wu, Ling Lin, Pu Ge, Jie Dai, Xiaojiao He, Kai Hu, Li Zhang
Increasing evidence suggests that the widely used antidiabetic drug metformin have an extensive therapeutic range beyond hypoglycemic therapy. We previously found that metformin significantly attenuated acute hepatitis. The present study investigated the potential effects of metformin on carbon tetrachloride (CCl4)-induced liver fibrosis in mice. The results indicated that treatment with metformin suppressed CCl4-induced elevation of liver index, formation of fibrotic septa, accumulation of connective tissue and upregulation of collagen I...
June 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28386343/signaling-by-tgf-betas-in-tubule-cultures-of-adult-rat-testis
#8
Kai-Hui Chan, Sebastian P Galuska, Pradeep Kumar Kudipudi, Mohammad Assad Riaz, Kate L Loveland, Lutz Konrad
Although signal transduction of transforming growth factor-betas (TGF-βs) is well characterized in individual cell types, data about TGF-β signaling in a cellular context is still scarce. In this study, we used ex vivo tubule cultures from adult rat testis to investigate TGF-β signaling. We show for the first time in testicular tubules, that TGF-βs also signal via the BMP type I receptors, with ALK2 used by TGF-β1 and ALK3 and ALK6 by TGF-β2. This signal transduction is mediated via Smad3 as well as via Smad1...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28356485/down-regulation-of-microrna-216b-inhibits-il-1%C3%AE-induced-chondrocyte-injury-by-up-regulation-of-smad3
#9
Jiye He, Jiahong Zhang, Dongliang Wang
Osteoarthritis (OA) is the most common type of joint disease, leading to a major cause of pain and disability. OA is characterized by the continuous degradation of articular cartilage, mainly resulting in an imbalance between synthesis and degradation of articular chondrocyte extracellular matrix (ECM). Aberrant miR-216b expression has been found in multiple cancers. However, the level of miR-216b in OA cartilage and its role in progression of this disease are still unknown. In the present study, the functional roles of miR-216b and its expression in OA tissues and interleukin-1β (IL-1β)-induced chondrocytes were examined...
April 30, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28324043/reduced-transforming-growth-factor-%C3%AE-activity-in-the-endometrium-of-women-with-heavy-menstrual-bleeding
#10
Jacqueline A Maybin, Lyndsey Boswell, Vicky J Young, William C Duncan, Hilary O D Critchley
Context: Heavy menstrual bleeding (HMB) is common and incapacitating. Aberrant menstrual endometrial repair may result in HMB. The transforming growth factor (TGF)-β superfamily contributes to tissue repair, but its role in HMB is unknown. Objective: We hypothesized that TGF-β1 is important for endometrial repair, and women with HMB have aberrant TGF-β1 activity at menses. Participants/Setting: Endometrial biopsies were collected from women, and menstrual blood loss objectively measured [HMB >80 mL/cycle; normal menstrual bleeding (NMB) <80 mL]...
April 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28303407/evodiamine-attenuates-tgf-%C3%AE-1-induced-fibroblast-activation-and-endothelial-to-mesenchymal-transition
#11
Qing-Qing Wu, Yang Xiao, Xiao-Han Jiang, Yuan Yuan, Zheng Yang, Wei Chang, Zhou-Yan Bian, Qi-Zhu Tang
The aim of this study is to investigate the effect of evodiamine on fibroblast activation in cardiac fibroblasts and endothelial to mesenchymal transition (EndMT) in human umbilical vein endothelial cells (HUVECs). Neonatal rat cardiac fibroblasts were stimulated with transforming growth factor beta 1 (TGF-β1) to induce fibroblast activation. After co-cultured with evodiamine (5, 10 μM), the proliferation and pro-fibrotic proteins expression of cardiac fibroblasts were evaluated. HUVECs were also stimulated with TGF-β1 to induce EndMT and treated with evodiamine (5, 10 μM) at the same time...
March 16, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28225655/mnte-2-pyp-treatment-or-nox4-inhibition-protects-against-radiation-induced-damage-in-mouse-primary-prostate-fibroblasts-by-inhibiting-the-tgf-beta-1-signaling-pathway
#12
Arpita Chatterjee, Elizabeth A Kosmacek, Rebecca E Oberley-Deegan
Prostate cancer patients who undergo radiotherapy frequently suffer from side effects caused by radiation-induced damage to normal tissues adjacent to the tumor. Exposure of these normal cells during radiation treatment can result in tissue fibrosis and cellular senescence, which ultimately leads to postirradiation-related chronic complications including urinary urgency and frequency, erectile dysfunction, urethral stricture and incontinence. Radiation-induced reactive oxygen species (ROS) have been reported as the most potent causative factor for radiation damage to normal tissue...
March 2017: Radiation Research
https://www.readbyqxmd.com/read/28108836/smad-dependent-signaling-plays-a-detrimental-role-in-a-fly-model-of-smarcb1-deficiency-and-the-biology-of-atypical-teratoid-rhabdoid-tumors
#13
Astrid Jeibmann, Jacqueline Schulz, Kristin Eikmeier, Pascal D Johann, Katharina Thiel, Isabel Tegeder, Oliver Ambrée, Michael C Frühwald, Stefan M Pfister, Marcel Kool, Werner Paulus, Martin Hasselblatt
Atypical teratoid/rhabdoid tumors (ATRT) are highly malignant brain tumors arising in young children. The majority of ATRT is characterized by inactivation of the chromatin remodeling complex member SMARCB1 (INI1/hSNF5). Little is known, however, on downstream pathways involved in the detrimental effects of SMARCB1 deficiency which might also represent targets for treatment. Using Drosophila melanogaster and the Gal4-UAS system, modifier screens were performed in order to identify the role of SMAD dependent signaling in the lethal phenotype associated with knockdown of snr1, the fly homolog of SMARCB1...
January 20, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28107544/cutaneous-hpv8-and-mmupv1-e6-proteins-target-the-notch-and-tgf-%C3%AE-tumor-suppressors-to-inhibit-differentiation-and-sustain-keratinocyte-proliferation
#14
Jordan M Meyers, Aayushi Uberoi, Miranda Grace, Paul F Lambert, Karl Munger
Cutaneous beta-papillomaviruses are associated with non-melanoma skin cancers that arise in patients who suffer from a rare genetic disorder, Epidermodysplasia verruciformis (EV) or after immunosuppression following organ transplantation. Recent studies have shown that the E6 proteins of the cancer associated beta human papillomavirus (HPV) 5 and HPV8 inhibit NOTCH and TGF-β signaling. However, it is unclear whether disruption of these pathways may contribute to cutaneous HPV pathogenesis and carcinogenesis...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28039556/microrna-15b-silencing-inhibits-il-1%C3%AE-induced-extracellular-matrix-degradation-by-targeting-smad3-in-human-nucleus-pulposus-cells
#15
Liang Kang, Cao Yang, Huipeng Yin, Kangcheng Zhao, Wei Liu, Wenbin Hua, Kun Wang, Yu Song, Ji Tu, Shuai Li, Rongjin Luo, Yukun Zhang
OBJECTIVES: To determine the role of microRNA-15b (miR-15b) in interleukin-1 beta (IL-1β)-induced extracellular matrix (ECM) degradation in the nucleus pulposus (NP). RESULTS: MiR-15b was up-regulated in degenerative NP tissues and in IL-1β-stimulated NP cells, as compared to the levels in normal controls (normal tissue specimens from patients with idiopathic scoliosis). Bioinformatics and luciferase activity analyses showed that mothers against decapentaplegic homolog 3 (SMAD3), a key mediator of the transforming growth factor-β signaling pathway, was directly targeted by miR-15b...
April 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/27906182/bcl-3-regulates-tgf%C3%AE-signaling-by-stabilizing-smad3-during-breast-cancer-pulmonary-metastasis
#16
Xi Chen, Xinwei Cao, Xiaohua Sun, Rong Lei, Pengfei Chen, Yongxu Zhao, Yuhang Jiang, Jie Yin, Ran Chen, Deji Ye, Qi Wang, Zhanjie Liu, Sanhong Liu, Chunyan Cheng, Jie Mao, Yingyong Hou, Mingliang Wang, Ulrich Siebenlist, Y Eugene Chin, Ying Wang, Liu Cao, Guohong Hu, Xiaoren Zhang
Transforming growth factor beta (TGFβ) signaling in breast cancer is selectively associated with pulmonary metastasis. However, the underlying mechanisms remain unclear. Here we show that Bcl-3, a member of the IκB family, serves as a critical regulator in TGFβ signaling to modulate breast cancer pulmonary metastasis. Bcl-3 expression was significantly associated with metastasis-free survival in breast cancer patients. Bcl-3 deletion inhibited the migration and invasion of breast cancer cells in vitro, as well as breast cancer lung metastasis in vivo...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27880821/inhibition-of-the-tgf%C3%AE-pathway-enhances-retinal-regeneration-in-adult-zebrafish
#17
Christoph Tappeiner, Ellinor Maurer, Pauline Sallin, Thomas Bise, Volker Enzmann, Markus Tschopp
In contrast to the mammalian retina, the zebrafish retina exhibits the potential for lifelong retinal neurogenesis and regeneration even after severe damage. Previous studies have shown that the transforming growth factor beta (TGFβ) signaling pathway is activated during the regeneration of different tissues in the zebrafish and is needed for regeneration in the heart and the fin. In this study, we have investigated the role of the TGFβ pathway in the N-methyl-N-nitrosourea (MNU)-induced chemical model of rod photoreceptor de- and regeneration in adult zebrafish...
2016: PloS One
https://www.readbyqxmd.com/read/27835939/anti-fibrotic-action-of-pirfenidone-in-dupuytren-s-disease-derived-fibroblasts
#18
Chaoming Zhou, Fang Liu, Phillip H Gallo, Mark E Baratz, Sandeep Kathju, Latha Satish
BACKGROUND: Dupuytren's disease (DD) is a complex fibro-proliferative disorder of the hand that is often progressive and eventually can cause contractures of the affected fingers. Transforming growth factor beta (TGF-β1) has been implicated as a key stimulator of myofibroblast activity and fascial contraction in DD. Pirfenidone (PFD) is an active small molecule shown to inhibit TGF-β1-mediated action in other fibrotic disorders. This study investigates the efficacy of PFD in vitro in inhibiting TGF-β1-mediated cellular functions leading to Dupuytren's fibrosis...
November 11, 2016: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/27703224/gallic-acid-prevents-isoproterenol-induced-cardiac-hypertrophy-and-fibrosis-through-regulation-of-jnk2-signaling-and-smad3-binding-activity
#19
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/27696331/tgf-beta-receptor-mediated-telomerase-inhibition-telomere-shortening-and-breast-cancer-cell-senescence
#20
Lucy Cassar, Craig Nicholls, Alex R Pinto, Ruping Chen, Lihui Wang, He Li, Jun-Ping Liu
Human telomerase reverse transcriptase (hTERT) plays a central role in telomere lengthening for continuous cell proliferation, but it remains unclear how extracellular cues regulate telomerase lengthening of telomeres. Here we report that the cytokine bone morphogenetic protein-7 (BMP7) induces the hTERT gene repression in a BMPRII receptor- and Smad3-dependent manner in human breast cancer cells. Chonic exposure of human breast cancer cells to BMP7 results in short telomeres, cell senescence and apoptosis...
January 2017: Protein & Cell
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