Read by QxMD icon Read

Smad3 AND Metformin

Ke Li, Ting-Ting Zhang, Fang Hua, Zhuo-Wei Hu
Deregulation of metabolism during melanoma progression is tightly associated with the genetic and epigenetic alterations of metabolic regulators. Metformin, a macroautophagy/autophagy inducer, has beneficial effects of preventing and treating multiple cancers with an unclear mechanism. Enhanced pseudokinase TRIB3 was reported to link metabolic stressors to melanoma promotion by inhibiting autophagy and ubiquitin-proteasome degradation systems. Here, we discuss our recent findings regarding how metformin reduces TRIB3 expression to restore autophagic flux and suppress melanoma progression in non-diabetic and diabetic mice...
June 21, 2018: Autophagy
Muyun Wei, Shaowei Mao, Guoliang Lu, Liang Li, Xiaopeng Lan, Zhongxian Huang, Yougen Chen, Miaoqing Zhao, Yueran Zhao, Qinghua Xia
BACKGROUND: Metformin (Met) is a widely available diabetic drug and shows suppressed effects on renal cell carcinoma (RCC) metabolism and proliferation. Laboratory studies in RCC suggested that metformin has remarkable antitumor activities and seems to be a potential antitumor drug. But the facts that metformin may be not effective in reducing the risk of RCC in cancer clinical trials made it difficult to determine the benefits of metformin in RCC prevention and treatment. The mechanisms underlying the different conclusions between laboratory experiments and clinical analysis remains unclear...
April 17, 2018: BMC Cancer
Ke Li, Ting-Ting Zhang, Feng Wang, Bing Cui, Chen-Xi Zhao, Jiao-Jiao Yu, Xiao-Xi Lv, Xiao-Wei Zhang, Zhao-Na Yang, Bo Huang, Xia Li, Fang Hua, Zhuo-Wei Hu
Metformin has beneficial effects of preventing and treating cancers on type 2 diabetic patients. However, the role of metformin in non-diabetic cancer patients and the precise molecular mechanisms against cancer have not yet been sufficiently elucidated. We recently reported that the pseudokinase protein TRIB3 acts as a stress sensor linking metabolic stressors to cancer promotion by inhibiting autophagy and ubiquitin-proteasomal degradation systems; genetically abrogating of TRIB3 expression reduces tumourigenesis and cancer progression...
March 9, 2018: Oncogene
Hao Yi, Chunling Huang, Ying Shi, Qinghua Cao, Yongli Zhao, Ling Zhang, Jason Chen, Carol A Pollock, Xin-Ming Chen
Progressive tubulointerstitial fibrosis has been recognized as a common pathological process that leads to the progression of all chronic kidney disease (CKD). Innovative strategies are needed to both prevent and treat CKD. Inflammatory and fibrotic signaling pathways play central roles in the progression of CKD regardless of aetiology. Hence, targeting inflammatory and fibrotic responses holds promise to limit renal fibrosis. Metformin has been the most prescribed glucose-lowering medicine worldwide, and its potential for many other therapeutic applications is also being explored intensively...
January 30, 2018: Journal of Cellular Physiology
Jinyang Wang, Yanbin Gao, Lijun Duan, Suhong Wei, Jing Liu, Liming Tian, Jinxing Quan, Qi Zhang, Juxiang Liu, Jinkui Yang
Insulin resistance (IR) plays a major role in the pathogenesis of abdominal obesity, hypertension, coronary heart disease, atherosclerosis and diabetes. miR-21 and TGF-β/smads is closely related to IR. However, it remained elusive whether metformin improved skeletal muscle insulin resistance (IRSM) by regulating miR-21 and its target signal TGF-β1/smads expression. In this study, high-fat diet rats with IR model and IR-skeletal muscle L6 cells (L6-SMCs) model were established, insulin sensitive index (ISI) and Homeostasis model assessment of IR (HOMA-IR) were applied, miR-21 and TGF-β1/smads mRNA expression were examined by RT-PCR, smad3 and smad7 protein were detected by western-blotting and laser scanning confocal microscopy (LSCM), the valid target of miR-21 was detected by luciferase reporter gene assay...
November 17, 2017: Oncotarget
Jian Wang, Ye Wang, Jun Han, Hong Mei, Dandan Yu, Qian Ding, Tao Zhang, Gang Wu, Gang Peng, Zhenyu Lin
While radiotherapy continues to be a major cancer treatment option, its dose-limiting side effects, such as pulmonary fibrosis, severely impair the quality of life in these patients. In this study, we evaluated the radioprotective effects of metformin, a commonly used biguanide antidiabetic medication, in a murine model of pulmonary damage. Sprague Dawley® rats received whole lung 20 Gy irradiation with or without metformin treatment. Computed tomography (CT) was performed and Hounsfield units (HU) were determined during the observation period...
July 2017: Radiation Research
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
Yenan Feng, Shuaixing Wang, Youyi Zhang, Han Xiao
Metformin is a well-known AMP-activated protein kinase (AMPK) activator, and it has been shown to inhibit organ fibrosis. Whether AMPKα2 mediates metformin protection against renal fibrosis remains unknown. Here, we aimed to investigate the role of the AMPKα2 isoform in mediating the inhibitory effect of metformin on renal fibrosis. Unilateral ureteral obstruction (UUO) was used to induce renal fibrosis in wild-type (WT) and AMPKα2 knockout (AMPKα2-/- ) mice. Metformin treatment was initiated 3 days before UUO and was continued until 7 days after UUO...
June 2017: Clinical and Experimental Pharmacology & Physiology
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...
November 2016: International Journal of Oncology
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
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
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
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
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
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
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
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"