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https://www.readbyqxmd.com/read/28549065/c-elegans-daf-16-foxo-interacts-with-tgf-%C3%A3-bmp-signaling-to-induce-germline-tumor-formation-via-mtorc1-activation
#1
Wenjing Qi, Yijian Yan, Dietmar Pfeifer, Erika Donner V Gromoff, Yimin Wang, Wolfgang Maier, Ralf Baumeister
Activation of the FOXO transcription factor DAF-16 by reduced insulin/IGF signaling (IIS) is considered to be beneficial in C. elegans due to its ability to extend lifespan and to enhance stress resistance. In the germline, cell-autonomous DAF-16 activity prevents stem cell proliferation, thus acting tumor-suppressive. In contrast, hypodermal DAF-16 causes a tumorous germline phenotype characterized by hyperproliferation of the germline stem cells and rupture of the adjacent basement membrane. Here we show that cross-talk between DAF-16 and the transforming growth factor ß (TGFß)/bone morphogenic protein (BMP) signaling pathway causes germline hyperplasia and results in disruption of the basement membrane...
May 26, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28548630/tenogenic-differentiation-of-human-embryonic-stem-cells
#2
Tina P Dale, Shazia Mazher, William R Webb, Jing Zhou, Nicola Maffulli, G-Q Chen, Alicia J El Haj, Nicholas R Forsyth
Tendon healing is complex to manage because of the limited regeneration capacity of tendon tissue; stem cell-based tissue engineering approaches may provide alternative healing strategies. We sought to determine whether human embryonic stem cells (hESC) could be induced to differentiate into tendon-like cells by the addition of exogenous bone morphogenetic protein (BMP)12 (growth differentiation factor(GDF)7) and BMP13 (GDF6). hESC (SHEF-1) were maintained with or without BMP12/13 supplementation, or supplemented with BMP12/13 and the SMAD signalling cascade blocking agent, dorsomorphin...
May 26, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28548248/the-emerging-role-of-interleukin-37-in-cardiovascular-diseases
#3
REVIEW
Xinyu Zhuang, Bangwei Wu, Jian Li, Haiming Shi, Bo Jin, Xinping Luo
INTRODUCTION: Interleukin (IL)-37 is a newly identified member of the IL-1 family, and shows a growing role in a variety of diseases. This review aims at summarizing and discussing the role of IL-37 in cardiovascular diseases. METHODS: Data for this review were identified by searches of MEDLINE, Embase, and PubMed using appropriate search terms. RESULTS: IL-37 is a newly identified cytokine belonging to the IL-1 family and is expressed in inflammatory immune cells and several parenchymal cells...
May 26, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28546962/recent-advances-of-curcumin-in-the-prevention-and-treatment-of-renal-fibrosis
#4
REVIEW
Xuejiao Sun, Yi Liu, Cheng Li, Xiting Wang, Ruyuan Zhu, Chenyue Liu, Haixia Liu, Lili Wang, Rufeng Ma, Min Fu, Dongwei Zhang, Yu Li
Curcumin, a polyphenol derived from the turmeric, has received attention as a potential treatment for renal fibrosis primarily because it is a relatively safe and inexpensive compound that contributes to kidney health. Here, we review the literatures on the applications of curcumin in resolving renal fibrosis in animal models and summarize the mechanisms of curcumin and its analogs (C66 and (1E,4E)-1,5-bis(2-bromophenyl) penta-1,4-dien-3-one(B06)) in preventing inflammatory molecules release and reducing the deposition of extracellular matrix at the priming and activation stage of renal fibrosis in animal models by consulting PubMed and Cnki databases over the past 15 years...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28546027/molecular-characterization-of-two-distinct-smads-gene-and-their-roles-in-the-response-to-bacteria-change-and-wound-healing-from-hyriopsis-cumingii
#5
Baoqing Hu, Peipei Yi, Zhenfang Li, Ming Zhang, Chungen Wen, Shaoqing Jian, Gang Yang
The proteins of Smad family are critical components of the TGF-β superfamily signal pathway. In this paper, we cloned two intracellular mediators of TGF-β signaling, Smad3 and Smad5, from the pearl mussel Hyriopsis cumingii. The full length cDNA of HcSmad3 and HcSmad5 were 2052 bp and 1908 bp and encoded two polypeptides of 418 and 461amino acid residues, respectively. The deduced amino acid of HcSmad3 and HcSmad5 possessed two putative conserved domains, MH1 and MH2, a conserved phosphorylation motif SSXS at the carboxyl-terminal...
May 22, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28544244/branched-chain-amino-acids-supplementation-modulates-tgf-%C3%AE-1-smad-signaling-pathway-and-interleukins-in-ccl4-induced-liver-fibrosis
#6
Naglaa F Khedr, Eman G Khedr
The alterations and low levels of circulating branched chain amino acids (BCAAs), leucine, isoleucine and valine, are associated with liver diseases. The study was designed to evaluate hepatoprotective effect of BCAAs on CCl4 -induced liver fibrosis and to investigate the molecular mechanisms underlying these effects in rats. Thirty male rats were divided into three groups. Control group (n=10), CCl4 group (n=10); rats were injected with CCl4 (1 mL/kg of 0.5:1 v/v injected i.p. twice weekly for 12 weeks). CCl4 +BCAAs group (n=10); rats were injected with similar doses of CCl4 and supplemented with a mixture of 600 mg/kg BCAAs (2: 1: 1...
May 23, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28542453/extracellular-calcium-promotes-bone-formation-from-bone-marrow-mesenchymal-stem-cells-by-amplifying-the-effects-of-bmp-2-on-smad-signalling
#7
Rubén Aquino-Martínez, Natalia Artigas, Beatriz Gámez, José Luis Rosa, Francesc Ventura
Understanding the molecular events that regulate osteoblast differentiation is essential for the development of effective approaches to bone regeneration. In this study, we analysed the osteoinductive properties of extracellular calcium in bone marrow-derived mesenchymal stem cell (BM-MSC) differentiation. We cultured BM-MSCs in 3D gelatin scaffolds with Ca2+ and BMP-2 as osteoinductive agents. Early and late osteogenic gene expression and bone regeneration in a calvarial critical-size defect model demonstrate that extracellular Ca2+ enhances the effects of BMP-2 on Osteocalcin, Runx2 and Osterix expression and promotes bone regeneration in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28540637/importance-of-human-peritoneal-mesothelial-cells-in-the-progression-fibrosis-and-control-of-gastric-cancer-inhibition-of-growth-and-fibrosis-by-tranilast
#8
Hiroto Saito, Sachio Fushida, Shinichi Harada, Tomoharu Miyashita, Katsunobu Oyama, Takahisa Yamaguchi, Tomoya Tsukada, Jun Kinoshita, Hidehiro Tajima, Itasu Ninomiya, Tetsuo Ohta
BACKGROUND: Scirrhous gastric cancer is an intractable disease with a high incidence of peritoneal dissemination and obstructive symptoms (e.g., ileus, jaundice, and hydronephrosis) arising from accompanying marked fibrosis. Microenvironmental interactions between cancer cells and cancer-associated fibroblasts are the suggested cause of the disease. We elucidated the mechanisms of tumor growth and fibrosis using human peritoneal mesothelial cells (HPMCs) and investigated the effects of tranilast treatment on cells and a xenograft mouse model of fibrosis...
May 24, 2017: Gastric Cancer
https://www.readbyqxmd.com/read/28539961/yiqi-huayu-jiedu-decoction-inhibits-the-invasion-and-metastasis-of-gastric-cancer-cells-through-tgf-%C3%AE-smad-pathway
#9
Ting-Ting Wu, Jun Lu, Pei-Qiu Zheng, Shen-Lin Liu, Jian Wu, Wei Sun, Qing-Min Sun, Nai-Xia Ma, Xue-Lian Ding, Min Chen, Xi Zou
Background. Yiqi Huayu Jiedu Decoction (YHJD) can obviously improve the quality of life of those patients with gastric cancer and prolong their survival. Methods. In vitro experiments, we observe YHJD's effect on the cells' proliferation by MTT assay. Cell adhesion assay, wound-healing assay, and Transwell invasion assay serve to detect its influence on cells' adhesion, migration, and invasion, respectively. Inhibitor (10 μM/L of SB431542) and activator (10 ng/mL of TGF-β) of TGF-β/Smad pathway were used to estimate whether YHJD's impact on the biological behavior of gastric cancer cells was related to TGF-β/Smad pathway...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28535536/losartan-preserves-erectile-function-by-suppression-of-apoptosis-and-fibrosis-of-corpus-cavernosum-and-corporal-veno-occlusive-dysfunction-in-diabetic-rats
#10
Wen Ji Li, Mingxi Xu, Meng Gu, Da-Chao Zheng, Jianhua Guo, Zhikang Cai, Zhong Wang
BACKGROUND/AIMS: Transforming growth factor-β1 (TGF-β1) plays important roles in penile corporal fibrosis and veno-occlusive dysfunction (CVOD). Angiotensin II (Ang II) is critically involved in erectile dysfunction, and blocking of Ang II is more important than inhibition of TGF-β in non-penile tissue fibrosis. However, the role of Ang II in corporal fbrosis and CVOD in a diabetic condition has not been investigated. METHODS: Diabetic rats were treated with sildenafil or losartan (an Ang II antagonist) alone or in combination...
May 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28534975/resveratrol-inactivates-pi3k-akt-signaling-through-upregulating-bmp7-in-human-colon-cancer-cells
#11
Yu-Hua Zeng, Lin-Yun Zhou, Qian-Zhao Chen, Yang Li, Ying Shao, Wen-Yan Ren, Yun-Peng Liao, Han Wang, Jia-Hui Zhu, Ming Huang, Fang He, Jin Wang, Ke Wu, Bai-Cheng He
Colon cancer is common worldwide and accounts for the significant cancer related morbidity and mortality in patients. Although extensive advancement has been made in colon cancer treatment and diagnosis in the last decades, there is still a giant gap between the clinical expectation. It has been reported that resveratrol (Res) may be a potential candidate for cancer treatment. However, the specific mechanism underlying this activity remains unclear. In this study, we investigated the anticancer activity of Res in human colon cancer cells, and unveiled the possible mechanism for this effect...
May 23, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28534517/prolonged-exposure-to-extracellular-lumican-restrains-pancreatic-adenocarcinoma-growth
#12
X Li, Y Kang, D Roife, Y Lee, M Pratt, M R Perez, B Dai, E J Koay, J B Fleming
We previously demonstrated that pancreatic stellate cells within pancreatic ductal adenocarcinoma (PDAC) stroma secrete lumican and its presence is associated with prolonged survival of patients with localized PDAC. Here, we observed that extracellular lumican decreases PDAC tumour cell growth in xenograft and syngeneic orthotopic animal models, and induces growth inhibition of low-passage human PDAC cells in a species-specific manner. PDAC cells grown in variant culture conditions and exposed to extracellular lumican display typical characterizations of cancer cell in a quiescent state, such as growth inhibition, apoptosis, G0/G1 arrest and chemoresistance...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28534511/stromal-derived-igf2-promotes-colon-cancer-progression-via-paracrine-and-autocrine-mechanisms
#13
C Unger, N Kramer, D Unterleuthner, M Scherzer, A Burian, A Rudisch, M Stadler, M Schlederer, D Lenhardt, A Riedl, S Walter, A Wernitznig, L Kenner, M Hengstschläger, J Schüler, W Sommergruber, H Dolznig
The insulin-like growth factor (IGF)2/IGF1 receptor (IGF1R) signaling axis has an important role in intestinal carcinogenesis and overexpression of IGF2 is an accepted risk factor for colorectal cancer (CRC) development. Genetic amplifications and loss of imprinting contribute to the upregulation of IGF2, but insufficiently explain the extent of IGF2 expression in a subset of patients. Here, we show that IGF2 was specifically induced in the tumor stroma of CRC and identified cancer-associated fibroblasts (CAFs) as the major source...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28530637/cell-penetrating-peptides-selectively-targeting-smad3-inhibit-profibrotic-tgf-%C3%AE-signaling
#14
Jeong-Han Kang, Mi-Yeon Jung, Xueqian Yin, Mahefatiana Andrianifahanana, Danielle M Hernandez, Edward B Leof
TGF-β is considered a master switch in the pathogenesis of organ fibrosis. The primary mediators of this activity are the SMAD proteins, particularly SMAD3. In the current study, we have developed a cell-penetrating peptide (CPP) conjugate of the HIV TAT protein that is fused to an aminoterminal sequence of sorting nexin 9 (SNX9), which was previously shown to bind phosphorylated SMAD3 (pSMAD3). We determined that specifically preventing the nuclear import of pSMAD3 using the TAT-SNX9 peptide inhibited profibrotic TGF-β activity in murine cells and human lung fibroblasts as well as in vivo with no demonstrable toxicity...
May 22, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28526296/mesenchymal-stem-cells-mscs-attenuate-cutaneous-sclerodermatous-graft-versus-host-disease-scl-gvhd-through-inhibition-of-immune-cell-infiltration-in-a-mouse-model
#15
Ji-Young Lim, Da-Bin Ryu, Sung-Eun Lee, Gyeongsin Park, Chang-Ki Min
Human chronic graft-versus-host disease (CGVHD) shares clinical characteristics with a murine sclerodermatous GVHD (Scl-GVHD) model that is characterized by skin thickening and lung fibrosis. A B10.D2 → BALB/c transplant model of Scl-GVHD was used to address the therapeutic effect of mesenchymal stem cells (MSCs) on the development of CGVHD. The clinical and pathological severity of cutaneous Scl-GVHD was significantly attenuated in MSC-treated recipients relative to Scl-GVHD controls. After MSC treatment, skin collagen production was significantly reduced with consistent downregulation of TGF-β expression...
May 16, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28524854/a-smad3-pten-regulatory-loop-controls-proliferation-and-apoptotic-responses-to-tgf-%C3%AE-in-mouse-endometrium
#16
Nuria Eritja, Isidre Felip, Mari Alba Dosil, Lucia Vigezzi, Cristina Mirantes, Andree Yeramian, Raúl Navaridas, Maria Santacana, David Llobet-Navas, Akihiko Yoshimura, Masatoshi Nomura, Mario Encinas, Xavier Matias-Guiu, Xavi Dolcet
The TGF-β/Smad and the PI3K/AKT signaling pathways are important regulators of proliferation and apoptosis, and their alterations lead to cancer development. TGF-β acts as a tumor suppressor in premalignant cells, but it is a tumor promoter for cancerous cells. Such dichotomous actions are dictated by different cellular contexts. Here, we have unveiled a PTEN-Smad3 regulatory loop that provides a new insight in the complex cross talk between TGF-β/Smad and PI3K/AKT signaling pathways. We demonstrate that TGF-β triggers apoptosis of wild-type polarized endometrial epithelial cells by a Smad3-dependent activation of PTEN transcription, which results in the inhibition of PI3K/AKT signaling pathway...
May 19, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28521467/upregulation-of-maspin-expression-in-human-cervical-carcinoma-cells-by-transforming-growth-factor-%C3%AE-1-through-the-convergence-of-smad-and-non-smad-signaling-pathways
#17
Ariyaphong Wongnoppavich, Nahathai Dukaew, Sirinthip Choonate, Kongthawat Chairatvit
Mammary serine protease inhibitor (maspin), encoded by the serpin family B member 5 gene, serves as a tumor suppressor through the inhibition of cancer cell invasion and metastasis. Paradoxically, maspin levels are upregulated in a number of types of malignant cells. Therefore, the regulation of maspin expression may depend on the genetic or epigenetic background and the specific microenvironment of carcinoma cells. In the present study, it was demonstrated that transforming growth factor β1 (TGF-β1) induced maspin expression at the transcript and protein levels in the human cervical carcinoma HeLa and human oral squamous carcinoma HSC4 cell lines...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28520219/plasminogen-activator-inhibitor-type-1-as-a-regulator-of-fibrosis
#18
Reyhaneh Rabieian, Maryam Boshtam, Mahshid Zareei, Shirin Kouhpayeh, Aria Masoudifar, Hamed Mirzaei
Fibrosis is known as a frequent and irreversible pathological condition which is associated with organ failure. Tissue fibrosis is a central process in a variety of chronic progressive diseases such as diabetes, hypertension, and persistent inflammation. This state could contribute to chronic injury and the initiation of tissue repair. Fibrotic disorders represent abnormal wound healing with defective matrix turnover and clearance that lead to excessive accumulation of extracellular matrix components. A variety of identified growth factors, cytokines, and persistently activated myofibroblasts have critical roles in the pathogenesis of fibrosis...
May 18, 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
#19
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/28512126/tumor-associated-myoepithelial-cells-promote-the-invasive-progression-of-ductal-carcinoma-in-situ-through-activation-of-tgf%C3%AE-signaling
#20
Pang-Kuo Lo, Yongshu Zhang, Yuan Yao, Benjamin Wolfson, Justine Yu, Shu-Yan Han, Nadire Duru, Qun Zhou
The normal myoepithelium has a tumor-suppressing nature and inhibits the progression of ductal carcinoma in situ (DCIS) into invasive ductal carcinoma (IDC). Conversely, a growing number of studies have shown that tumor-associated myoepithelial cells have a tumor-promoting effect. Moreover, the exact role of tumor-associated myoepithelial cells in the DCIS-to-IDC development remains undefined. To address this, we explored the role of tumor-associated myoepithelial cells in the DCIS-to-IDC progression. We developed a direct coculture system to study the cell-cell interactions between DCIS cells and tumor-associated myoepithelial cells...
May 16, 2017: Journal of Biological Chemistry
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