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https://www.readbyqxmd.com/read/28346732/asiaticoside-hinders-the-invasive-growth-of-keloid-fibroblasts-through-inhibition-of-the-gdf-9-mapk-smad-pathway
#1
Xin Wu, Difei Bian, Yannong Dou, Zhunan Gong, Qian Tan, Yufeng Xia, Yue Dai
Higher expression of growth differentiation factor-9 (GDF-9) in keloids compared with hypertrophic scars and normal skin tissues has been reported recently. The present study was performed to investigate the role of GDF-9 in keloid pathogenesis, and to elucidate its implication for asiaticoside in the keloid management. The data showed that GDF-9 could enhance the proliferation, migration, and invasion of keloid fibroblasts (KFs), while it only slightly elevated collagen expression, indicating that the effect of GDF-9 was opposite to that of TGF-β1...
March 27, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28345552/relationship-between-hepatitis-c-virus-infection-and-iron-overload
#2
REVIEW
Dong-Mei Zou, Wan-Ling Sun
OBJECTIVE: The aim of this study was to summarize the interactions between hepatitis C virus (HCV) infection and iron overload, and to understand the mechanisms of iron overload in chronic hepatitis C (CHC) and the role iron plays in HCV life cycle. DATA SOURCES: This review was based on data in articles published in the PubMed databases up to January 28, 2017, with the keywords "hepatitis C virus", "iron overload", "iron metabolism", "hepcidin", "translation", and "replication"...
April 5, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28345462/functional-interaction-of-fibroblast-growth-factor-8b-and-androgen-in-prostate-cancer-cell-proliferation
#3
Wen-Jun Xiao, Gui-Ming Zhang, Ding-Wei Ye
Fibroblast growth factor 8b and androgen play important roles in cell proliferation of prostate cancer. We investigated the effects of fibroblast growth factor 8b and androgen on the proliferation of prostate cell lines and the corresponding intracellular mechanisms. It is found that dihydrotestosterone and fibroblast growth factor 8b stimulated Lncap cell mitosis in a concentration-responsive manner, with 30 ng/mL as the most suitable concentration, respectively. Dihydrotestosterone treatment alone did not enhance the expression and phosphorylation level of fibroblast growth factor receptor but significantly enhanced the level of fibroblast growth factor receptor phosphorylation elicited by fibroblast growth factor 8b...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28343310/steroidogenic-genes-expressions-are-repressed-by-high-levels-of-leptin-and-the-jak-stat-signaling-pathway-in-ma-10-leydig-cells
#4
David A Landry, François Sormany, Josée Haché, Pauline Roumaud, Luc J Martin
The adipose tissue is an important endocrine organ secreting numerous peptide hormones, including leptin. Increased circulating levels of leptin, as a result of hormonal resistance in obese individuals, may contribute to lower androgen production in obese males. However, the molecular mechanisms involved need to be better defined. Androgens are mainly produced by Leydig cells within the testis. In male rodents, activation of the leptin receptor modulates a cascade of intracellular signal transduction pathways which may lead to regulation of transcription factors having influences on steroidogenesis in Leydig cells...
March 25, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28342289/tgf%C3%AE-taz-srf-signaling-regulates-vascular-smooth-muscle-cell-differentiation
#5
Christina Pagiatakis, Dandan Sun, Stephanie Wales Tobin, Tetsuaki Miyake, John C McDermott
Vascular smooth muscle cells (VSMCs) do not terminally differentiate; they modulate their phenotype between proliferative and differentiated states, which is a major factor contributing to vascular diseases. TGFβ signaling has been implicated in inducing VSMC differentiation, although the exact mechanism remains largely unknown. Our goal was to assess the network of transcription factors involved in the induction of VSMC differentiation, and to determine the role of TAZ in promoting the quiescent VSMC phenotype...
March 25, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28339457/targeted-aav5-smad7-gene-therapy-inhibits-corneal-scarring-in-vivo
#6
Suneel Gupta, Jason T Rodier, Ajay Sharma, Elizabeth A Giuliano, Prashant R Sinha, Nathan P Hesemann, Arkasubhra Ghosh, Rajiv R Mohan
Corneal scarring is due to aberrant activity of the transforming growth factor β (TGFβ) signaling pathway following traumatic, mechanical, infectious, or surgical injury. Altered TGFβ signaling cascade leads to downstream Smad (Suppressor of mothers against decapentaplegic) protein-mediated signaling events that regulate expression of extracellular matrix and myogenic proteins. These events lead to transdifferentiation of keratocytes into myofibroblasts through fibroblasts and often results in permanent corneal scarring...
2017: PloS One
https://www.readbyqxmd.com/read/28337441/pentoxifylline-regulates-plasminogen-activator-inhibitor-1-expression-and-protein-kinase-a-phosphorylation-in-radiation-induced-lung-fibrosis
#7
Jong-Geol Lee, Sehwan Shim, Min-Jung Kim, Jae Kyung Myung, Won-Suk Jang, Chang-Hwan Bae, Sun-Joo Lee, Kyeong Min Kim, Young-Woo Jin, Seung-Sook Lee, Sunhoo Park
Purpose. Radiation-induced lung fibrosis (RILF) is a serious late complication of radiotherapy. In vitro studies have demonstrated that pentoxifylline (PTX) has suppressing effects in extracellular matrix production in fibroblasts, while the antifibrotic action of PTX alone using clinical dose is yet unexplored. Materials and Methods. We used micro-computed tomography (micro-CT) and histopathological analysis to evaluate the antifibrotic effects of PTX in a rat model of RILF. Results. Micro-CT findings showed that lung density, volume loss, and mediastinal shift are significantly increased at 16 weeks after irradiation...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28336232/tgf%C3%AE-1-induces-endometrial-cancer-cell-adhesion-and-migration-by-up-regulating-integrin-%C3%AE-v%C3%AE-3-via-smad-independent-mek-erk1-2-signaling
#8
Siyuan Xiong, Christian Klausen, Jung-Chien Cheng, Peter C K Leung
Endometrial cancer is the most common, and second most lethal, gynecological malignancy, and its rates of incidence and death are growing. This is likely attributable to increased numbers of high-risk type II endometrial cancers which account for ~30% of cases but ~75% of deaths due to their aggressive and metastatic behaviour. Histopathological and in vitro functional studies suggest that aberrant TGFβ1 signaling may contribute to endometrial cancer development and the acquisition of invasive/metastatic characteristics...
March 21, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28335084/identification-of-new-bmp6-pro-peptide-mutations-in-patients-with-iron-overload
#9
Chiara Piubelli, Annalisa Castagna, Giacomo Marchi, Monica Rizzi, Fabiana Busti, Sadaf Badar, Monia Marchetti, Marco De Gobbi, Antonella Roetto, Luciano Xumerle, Eda Suku, Alejandro Giorgetti, Massimo Delledonne, Oliviero Olivieri, Domenico Girelli
Hereditary Hemochromatosis (HH) is a genetically heterogeneous disorder caused by mutations in at least 5 different genes (HFE, HJV, TFR2, SLC40A1, HAMP) involved in the production or activity of the liver hormone hepcidin, a key regulator of systemic iron homeostasis. Nevertheless, patients with an HH-like phenotype that remains completely/partially unexplained despite extensive sequencing of known genes are not infrequently seen at referral centers, suggesting a role of still unknown genetic factors. A compelling candidate is Bone Morphogenetic Protein 6 (BMP6), which acts as a major activator of the BMP-SMAD signaling pathway, ultimately leading to the upregulation of hepcidin gene transcription...
March 23, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28325473/foxh1-occupies-cis-regulatory-modules-prior-to-dynamic-transcription-factor-interactions-controlling-the-mesendoderm-gene-program
#10
Rebekah M Charney, Elmira Forouzmand, Jin Sun Cho, Jessica Cheung, Kitt D Paraiso, Yuuri Yasuoka, Shuji Takahashi, Masanori Taira, Ira L Blitz, Xiaohui Xie, Ken W Y Cho
The interplay between transcription factors and chromatin dictates gene regulatory network activity. Germ layer specification is tightly coupled with zygotic gene activation and, in most metazoans, is dependent upon maternal factors. We explore the dynamic genome-wide interactions of Foxh1, a maternal transcription factor that mediates Nodal/TGF-β signaling, with cis-regulatory modules (CRMs) during mesendodermal specification. Foxh1 marks CRMs during cleavage stages and recruits the co-repressor Tle/Groucho in the early blastula...
March 27, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28324043/reduced-transforming-growth-factor-beta-activity-in-the-endometrium-of-women-with-heavy-menstrual-bleeding
#11
J A Maybin, L Boswell, V J Young, W C Duncan, Hod Critchley
Context: Heavy menstrual bleeding (HMB) is common and incapacitating. Aberrant menstrual endometrial repair may result in HMB. The TGFβ superfamily contributes to tissue repair, but its role in HMB is unknown. Objective: We hypothesised that TGFβ1 is important for endometrial repair and women with HMB have aberrant TGFβ1 activity at menses. Participants/Setting: Endometrial biopsies were collected from women and menstrual blood loss objectively measured (HMB >80ml/cycle, normal menstrual bleeding, NMB <80ml)...
January 3, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28322831/chemical-inhibitors-of-c-met-receptor-tyrosine-kinase-stimulate-osteoblast-differentiation-and-bone-regeneration
#12
Jung-Woo Kim, Mi Nam Lee, Byung-Chul Jeong, Sin-Hye Oh, Min-Suk Kook, Jeong-Tae Koh
The c-Met receptor tyrosine kinase and its ligand, hepatocyte growth factor (HGF), have been recently introduced to negatively regulate bone morphogenetic protein (BMP)-induced osteogenesis. However, the effect of chemical inhibitors of c-Met receptor on osteoblast differentiation process has not been examined, especially the applicability of c-Met chemical inhibitors on in vivo bone regeneration. In this study, we demonstrated that chemical inhibitors of c-Met receptor tyrosine kinase, SYN1143 and SGX523, could potentiate the differentiation of precursor cells to osteoblasts and stimulate regeneration in calvarial bone defects of mice...
March 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28320972/sensing-relative-signal-in-the-tgf-%C3%AE-smad-pathway
#13
Christopher L Frick, Clare Yarka, Harry Nunns, Lea Goentoro
How signaling pathways function reliably despite cellular variation remains a question in many systems. In the transforming growth factor-β (Tgf-β) pathway, exposure to ligand stimulates nuclear localization of Smad proteins, which then regulate target gene expression. Examining Smad3 dynamics in live reporter cells, we found evidence for fold-change detection. Although the level of nuclear Smad3 varied across cells, the fold change in the level of nuclear Smad3 was a more precise outcome of ligand stimulation...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28320106/ctrp3-attenuates-hepatic-stellate-cell-activation-through-transforming-growth-factor-%C3%AE-smad-signaling-pathway
#14
Chuantao Cheng, Shuo Yu, Ran Kong, Qinggong Yuan, Yuefeng Ma, Wenbin Yang, Gang Cao, Liyi Xie
Activation of hepatic stellate cells (HSCs) plays a pivotal role in the development of liver fibrosis. C1q/tumor necrosis factor-related protein 3 (CTRP3), a member of CTRPs, was involved in fibrosis. However, little is known about the role of CTRP3 in liver fibrosis. This study aimed to determine its role in liver fibrosis and explore the possible mechanism. Our results demonstrated that CTRP3 was lowly expressed in liver fibrosis tissues and activated HSCs. Overexpression of CTRP3 inhibited the proliferation and migration of HSCs, as well as suppressed the expression of extracellular matrix (ECM) in transforming growth factor-β1 (TGF-β1)-stimulated HSC-T6 cells...
March 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28320097/asiatic-acid-ameliorates-pulmonary-fibrosis-induced-by-bleomycin-blm-via-suppressing-pro-fibrotic-and-inflammatory-signaling-pathways
#15
Shu-Hong Dong, Yan-Wei Liu, Feng Wei, Hui-Zhen Tan, Zhi-Dong Han
Idiopathic pulmonary fibrosis is known as a life-threatening disease with high mortality and limited therapeutic strategies. In addition, the molecular mechanism by which pulmonary fibrosis developed is not fully understood. Asiatic acid (AA) is a triterpenoid, isolated from Centella asiatica, exhibiting efficient anti-inflammatory and anti-oxidative activities. In our study, we attempted to explore the effect of Asiatic acid on bleomycin (BLM)-induced pulmonary fibrosis in mice. The findings indicated that pre-treatment with Asiatic acid inhibited BLM-induced lung injury and fibrosis progression in mice...
March 17, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28319248/cyclic-tensile-strain-enhances-human-mesenchymal-stem-cell-smad-2-3-activation-and-tenogenic-differentiation-in-anisotropic-collagen-glycosaminoglycan-scaffolds
#16
W G Grier, A S Moy, B A Harley
Stem cell research arose from the need to explore new therapeutic possibilities for intractable and lethal diseases. Although musculoskeletal disorders are basically nonlethal, their high prevalence and relative ease of performing clinical trials have facilitated the clinical application of stem cells in this field. However, few reliable clinical studies have been published, despite the plethora of in vitro and preclinical studies in stem cell research for regenerative medicine in the musculoskeletal system...
March 20, 2017: European Cells & Materials
https://www.readbyqxmd.com/read/28318631/the-antihelmenthic-phosphate-niclosamide-impedes-renal-fibrosis-by-inhibiting-homeodomain-interacting-protein-kinase-2-expression
#17
Xiaoyan Chang, Xin Zhen, Jixing Liu, Xiaomei Ren, Zheng Hu, Zhanmei Zhou, Fengxin Zhu, Ke Ding, Jing Nie
Renal fibrosis is the final common pathway of all varieties of progressive chronic kidney disease. However, there are no effective therapies to prevent or slow the progression of renal fibrosis. Niclosamide is a US Food and Drug Administration-approved oral antihelminthic drug used for treating most tapeworm infections. Here, we demonstrated that phosphate niclosamide, the water-soluble form of niclosamide, significantly reduced proteinuria, glomerulosclrotic lesions, and interstitial fibrosis in a murine model of adriamycin nephropathy...
March 16, 2017: Kidney International
https://www.readbyqxmd.com/read/28316163/-effects-of-silencing-smad-ubiquitination-regulatory-factor-2-on-the-function-of-human-hypertrophic-scar-derived-fibroblasts
#18
Z Zhang, F Kuang, C L Liu, B Chen, W B Tang, X J Li
Objective: To explore the effects of silencing Smad ubiquitination regulatory factor 2 (Smurf2) on the secretion of transforming growth factor beta 1 (TGF-β(1)), alpha-smooth muscle actin (α-SMA), and collagen type Ⅰ by human hypertrophic scar-derived fibroblasts. Methods: The human normal skin-derived fibroblasts and hypertrophic scar-derived fibroblasts were cultured with explant culture technique from the normal skin and hypertrophic scar tissue, which was obtained from 9 patients with hypertrophic scars after burn...
March 20, 2017: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/28315766/bone-morphogenetic-protein-4-is-overexpressed-in-and-promotes-migration-and-invasion-of-drug-resistant-cancer-cells
#19
Kairui Zhou, Xiaoli Shi, Jinling Huo, Weihua Liu, Dongxiao Yang, Tengjiao Yang, Tiantian Qin, Cong Wang
Drug resistance and metastasis significantly hinder chemotherapy and worsen prognoses in cancer. Bone morphogenetic protein 4 (BMP4) belongs to the TGF-β superfamily, has broad biological activities in cell proliferation and cartilage differentiation and is also able to induce migration and invasion. Herein, we investigated the role of BMP4 in the regulation of metastasis in paclitaxel-resistant human esophageal carcinoma EC109 cells (EC109/Taxol) and docetaxel-resistant human gastric cancer MGC803 cells (MGC/Doc)...
March 15, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28315487/xpln-is-modulated-by-hdac-inhibitors-and-negatively-regulates-sparc-expression-by-targeting-mtorc2-in-human-lung-fibroblasts
#20
Koichiro Kamio, Arata Azuma, Jiro Usuki, Kuniko Matsuda, Minoru Inomata, Nobuhiko Nishijima, Shioto Itakura, Hiroki Hayashi, Takeru Kashiwada, Nariaki Kokuho, Kenichiro Atsumi, Tomoyoshi Yamaguchi, Kazue Fujita, Yoshinobu Saito, Shinji Abe, Kaoru Kubota, Akihiko Gemma
Pathogenesis of idiopathic pulmonary fibrosis (IPF) remains unclear. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that participates in the assembly and turnover of the extracellular matrix, whose expression is regulated by transforming growth factor (TGF)-β1 through activation of mammalian target of rapamycin complex 2 (mTORC2). Exchange factor found in platelets, leukemic, and neuronal tissues (XPLN) is an endogenous inhibitor of mTORC2. However, whether XPLN modulates SPARC expression remains unknown...
March 14, 2017: Pulmonary Pharmacology & Therapeutics
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