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Smad3 AND Metformin

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https://www.readbyqxmd.com/read/27599468/metformin-inhibits-the-radiation-induced-invasive-phenotype-of-esophageal-squamous-cell-carcinoma
#1
Akira Nakayama, Itasu Ninomiya, Shinichi Harada, Tomoya Tsukada, Koichi Okamoto, Shinichi Nakanuma, Seisho Sakai, Isamu Makino, Jun Kinoshita, Hironori Hayashi, Katsunobu Oyama, Tomoharu Miyashita, Hidehiro Tajima, Hiroyuki Takamura, Sachio Fushida, Tetsuo Ohta
Esophageal cancer is one of the most aggressive tumor types because of its invasiveness and metastatic potential. Several reports have described an association between increased invasiveness after ionizing radiation (IR) treatment and epithelial-to-mesenchymal transition (EMT). The biguanide metformin is reported to prevent transforming growth factor-β (TGF-β)-induced EMT and proliferation of cancer. This study examined whether IR induces EMT and promotes the invasive potential of TE-9 esophageal squamous cell carcinoma cells and the effect of metformin on IR-induced EMT...
August 31, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27207538/ampk-activation-by-metformin-suppresses-abnormal-extracellular-matrix-remodeling-in-adipose-tissue-and-ameliorates-insulin-resistance-in-obesity
#2
Ting Luo, Allison Nocon, Jessica Fry, Alex Sherban, Xianliang Rui, Bingbing Jiang, X Julia Xu, Jingyan Han, Yun Yan, Qin Yang, Qifu Li, Mengwei Zang
Fibrosis is emerging as a hallmark of metabolically dysregulated white adipose tissue (WAT) in obesity. Although adipose tissue fibrosis impairs adipocyte plasticity, little is known about how aberrant extracellular matrix (ECM) remodeling of WAT is initiated during the development of obesity. Here we show that treatment with the antidiabetic drug metformin inhibits excessive ECM deposition in WAT of ob/ob mice and mice with diet-induced obesity, as evidenced by decreased collagen deposition surrounding adipocytes and expression of fibrotic genes including the collagen cross-linking regulator LOX Inhibition of interstitial fibrosis by metformin is likely attributable to the activation of AMPK and the suppression of transforming growth factor-β1 (TGF-β1)/Smad3 signaling, leading to enhanced systemic insulin sensitivity...
August 2016: Diabetes
https://www.readbyqxmd.com/read/26984042/drug-resistance-originating-from-a-tgf-%C3%AE-fgf-2-driven-epithelial-to-mesenchymal-transition-and-its-reversion-in-human-lung-adenocarcinoma-cell-lines-harboring-an-egfr-mutation
#3
Ryota Kurimoto, Shunichiro Iwasawa, Takahiro Ebata, Tsukasa Ishiwata, Ikuo Sekine, Yuji Tada, Koichiro Tatsumi, Shuhei Koide, Atsushi Iwama, Yuichi Takiguchi
Epithelial-to-mesenchymal transition (EMT) is a malignant cancer phenotype characterized by augmented invasion and metastasis, chemoresistance, and escape from host-immunity. This study sought to identify efficient methods for inducing EMT reversion, to evaluate alterations in chemosensitivity and immune-protectiveness, and to elucidate the underlying mechanisms. In this study, the human lung adenocarcinoma cell lines PC-9 and HCC-827, harboring an EGFR mutation, were treated with TGF-β and FGF-2 to induce EMT...
May 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/25744403/activation-of-ampk-by-metformin-inhibits-tgf-%C3%AE-induced-collagen-production-in-mouse-renal-fibroblasts
#4
Jiamei Lu, Jianhua Shi, Manxiang Li, Baosong Gui, Rongguo Fu, Ganglian Yao, Zhaoyang Duan, Zhian Lv, Yanyan Yang, Zhao Chen, Lining Jia, Lifang Tian
AIMS: To clarify whether activation of adenosine monophosphate-activated protein kinase (AMPK) by metformin inhibits transforming growth factor beta (TGF-β)-induced collagen production in primary cultured mouse renal fibroblasts and further to address the molecular mechanisms. MAIN METHODS: Primary cultured mouse renal fibroblasts were stimulated with TGF-β1 and the sequence specific siRNA of Smad3 or connective tissue growth factor (CTGF) was applied to investigate the involvement of these molecular mediators in TGF-β1-induced collagen type I production...
April 15, 2015: Life Sciences
https://www.readbyqxmd.com/read/25462562/metformin-enhances-the-anti-adipogenic-effects-of-atorvastatin-via-modulation-of-stat3-and-tgf-%C3%AE-smad3-signaling
#5
Byung-Hak Kim, Songhee Han, Haeri Lee, Chi Hye Park, Young Mee Chung, Kyungmin Shin, Hyun Gyu Lee, Sang-Kyu Ye
Adipocyte accumulation is associated with the development of obesity and obesity-related diseases. Interactions of master transcription factors and signaling cascades are required for adipogenesis. Regulation of excessive adipogenic processes may be an attractive therapeutic for treatment of obesity and obesity-related diseases. In this study, we found that atorvastatin exerts an anti-adipogenic activity in 3T3-L1 pre-adipocytes, and that this activity is elevated in combination with metformin. Expression of the adipogenic master regulators PPARγ and C/EBPα, and their target gene aP2, was suppressed by atorvastatin...
January 2, 2015: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/21567395/amp-activated-protein-kinase-inhibits-tgf-%C3%AE-induced-fibrogenic-responses-of-hepatic-stellate-cells-by-targeting-transcriptional-coactivator-p300
#6
Joong-Yeon Lim, Min-A Oh, Won Ho Kim, Hee-Young Sohn, Sang Ick Park
Liver fibrosis is a common consequence of various chronic liver injuries, including virus infection and ethanol. Activated hepatic stellate cells (HSCs) contribute to liver fibrosis through the accumulation of extracellular matrix proteins, including type I alpha collagen (COL1A). The activation of adenosine monophosphate-activated protein kinase (AMPK) modulates HSCs activation, but its underlying mechanism remains unclear. Here, we report that AMPK inhibits transforming growth factor (TGF)-β-induced fibrogenic property of HSCs by regulating transcriptional coactivator p300...
March 2012: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/21560355/-effects-of-sericine-on-tgf-beta1-smad3-signal-pathway-of-diabetic-mephropathy-rats-kidney
#7
Cheng-Jun Song, Xiu-Mei Fu, Jian Li, Zhi-Hong Chen
OBJECTIVE: To observe the effects of color silk cocoon extraction-sericine on transforming growth factor-beta1 (TGF-beta1) and Smad3 protein expression in kidney of diabetic nephropathy (DN) rats. METHODS: 60 male SD rats were randomly divided into 5 groups (n = 12): normal control group, DN model group, sericine treatment group, metformin group and sericine prevention group. The rats in model group, sericine treatment group, metformin group and sericine prevention group were all established DN rats model by intraperitoneally injected streptozotocin (STZ)...
February 2011: Chinese Journal of Applied Physiology
https://www.readbyqxmd.com/read/20200042/metformin-attenuates-cardiac-fibrosis-by-inhibiting-the-tgfbeta1-smad3-signalling-pathway
#8
Han Xiao, Xiaowei Ma, Wei Feng, Yongnan Fu, Zhizhen Lu, Ming Xu, Qiang Shen, Yi Zhu, Youyi Zhang
AIMS: The mechanism of the cardioprotective action of metformin is incompletely understood. We determined the role of metformin in cardiac fibrosis and investigated the mechanism. METHODS AND RESULTS: Ten-week-old male mice (C57BL/6) were subjected to left ventricular pressure overload by transverse aortic constriction. Mice received metformin (200 mg/kg/day) or normal saline for 6 weeks. Metformin inhibited cardiac fibrosis (fibrosis area/total heart area: 0.6 +/- 0...
August 1, 2010: Cardiovascular Research
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