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https://www.readbyqxmd.com/read/28239053/transforming-growth-factor-beta-and-forkhead-box-o-transcription-factors-as-cardiac-fibroblast-regulators
#1
Ignacio Norambuena-Soto, Constanza Núñez-Soto, Fernanda Sanhueza-Olivares, Nicole Cancino-Arenas, David Mondaca-Ruff, Raul Vivar, Guillermo Díaz-Araya, Rosemarie Mellado, Mario Chiong
Fibroblasts play several homeostatic roles, including electrical coupling, paracrine signaling and tissue repair after injury. Fibroblasts have low secretory activity. However, in response to injury, they differentiate to myofibroblasts. These cells have an increased extracellular matrix synthesis and secretion, including collagen fibers, providing stiffness to the tissue. In pathological conditions myofibroblasts became resistant to apoptosis, remaining in the tissue, causing excessive extracellular matrix secretion and deposition, which contributes to the progressive tissue remodeling...
February 24, 2017: Bioscience Trends
https://www.readbyqxmd.com/read/28237615/inhibition-of-dna-methylation-in-the-col1a2-promoter-by-anacardic-acid-prevents-uv-induced-decrease-of-type-i-procollagen-expression
#2
Min-Kyoung Kim, Eun Ju Kim, Yao Cheng, Mi Hee Shin, Jang-Hee Oh, Dong Hun Lee, Jin Ho Chung
Ultraviolet (UV) radiation decreases type I procollagen production mainly by inhibiting the TGF-β/Smad signaling pathway. Because further epigenetic regulatory mechanisms are unclear, we investigated the roles of DNA methylation and histone acetylation in UV-induced regulation of collagen type I alpha 2 (COL1A2) transcription in human dermal fibroblasts(HDFs). Anacardic acid (AA), a p300 histone acetyltransferase inhibitor, rescued the UV-induced decrease of type I procollagen expression in HDFs. Although UV irradiation induced global histone acetylation, it reduced the local recruitment of histone H3 acetylation as well as p300, and Smad2/3 to the p300 binding site (-1406/-1393) in the COL1A2 promoter as shown by chromatin immunoprecipitation...
February 22, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28230313/crosstalk-between-smad2-3-and-specific-isoforms-of-erk-in-tgf-%C3%AE-1-induced-timp-3-expression-in-rat-chondrocytes
#3
Yanhui Zhu, Jianhua Gu, Tong Zhu, Chen Jin, Xiaopeng Hu, Xiang Wang
This study investigated the roles of ERK1 and ERK2 in transforming growth factor-β1 (TGF-β1)-induced tissue inhibitor of metalloproteinases-3 (TIMP-3) expression in rat chondrocytes, and the specific roles of ERK1 and ERK2 in crosstalk with Smad2/3 were investigated to demonstrate the molecular mechanism of ERK1/2 regulation of TGF-β1 signalling. To examine the interaction of specific isoforms of ERK and the Smad2/3 signalling pathway, chondrocytes were infected with LV expressing either ERK1 or ERK2 siRNA and stimulated with or without TGF-β1...
February 23, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28230206/mirna-21-mediates-the-antiangiogenic-activity-of-metformin-through-targeting-pten-and-smad7-expression-and-pi3k-akt-pathway
#4
Mao Luo, Xiaoyong Tan, Lin Mu, Yulin Luo, Rong Li, Xin Deng, Ni Chen, Meiping Ren, Yongjie Li, Liqun Wang, Jianbo Wu, Qin Wan
Metformin, an anti-diabetic drug commonly used for type 2 diabetes therapy, is associated with anti-angiogenic effects in conditions beyond diabetes. miR-21 has been reported to be involved in the process of angiogenesis. However, the precise regulatory mechanisms by which the metformin-induced endothelial suppression and its effects on miR-21-dependent pathways are still unclear. Bioinformatic analysis and identification of miR-21 and its targets and their effects on metformin-induced antiangiogenic activity were assessed using luciferase assays, quantitative real-time PCR, western blots, scratch assays, CCK-8 assays and tubule formation assays...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28229387/the-effects-of-cerium-valence-states-at-cerium-oxide-coatings-on-the-responses-of-bone-mesenchymal-stem-cells-and-macrophages
#5
Mingyu You, Kai Li, Youtao Xie, Liping Huang, Xuebin Zheng
Ideal orthopedic coatings should trigger good osteogenic response and limited inflammatory response. The cerium valence states in ceria are associated with their anti-oxidative activity and anti-inflammatory property. In the study, we prepared two kinds of plasma sprayed CeO2 coatings with different Ce(4+) concentrations to investigate the effects of Ce valence states on the response of bone mesenchymal stem cells (BMSCs) and macrophage RAW264.7. Both the coatings (CeO2-A and CeO2-B) were characterized via XRD, SEM, and X-ray photoelectron spectroscopy...
February 22, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28222740/dibutyryl-camp-attenuates-pulmonary-fibrosis-by-blocking-myofibroblast-differentiation-via-pka-creb-cbp-signaling-in-rats-with-silicosis
#6
Yan Liu, Hong Xu, Yucong Geng, Dingjie Xu, Lijuan Zhang, Yi Yang, Zhongqiu Wei, Bonan Zhang, Shifeng Li, Xuemin Gao, Ruimin Wang, Xianghong Zhang, Darrell Brann, Fang Yang
BACKGROUND: Myofibroblasts play a major role in the synthesis of extracellular matrix (ECM) and the stimulation of these cells is thought to play an important role in the development of silicosis. The present study was undertaken to investigate the anti-fibrotic effects of dibutyryl-cAMP (db-cAMP) on rats induced by silica. METHODS: A HOPE MED 8050 exposure control apparatus was used to create the silicosis model. Rats were randomly divided into 4 groups: 1)controls for 16 w; 2)silicosis for 16 w; 3)db-cAMP pre-treatment; 4) db-cAMP post-treatment...
February 21, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28218651/proteome-characteristics-of-non-alcoholic-steatohepatitis-liver-tissue-and-associated-hepatocellular-carcinomas
#7
Anna Kakehashi, Vasily E Stefanov, Naomi Ishii, Takahiro Okuno, Hideki Fujii, Kazuaki Kawai, Norifumi Kawada, Hideki Wanibuchi
To uncover mechanisms of nonalcoholic steatohepatitis (NASH) associated hepatocarcinogenesis, we compared the proteomes of human NASH-associated liver biopsies, resected hepatocellular carcinomas (HCCs) and HCCs of HCV⁺ patients with normal liver tissue of patients with gastrointestinal tumor metastasis, in formalin-fixed paraffin-embedded samples obtained after surgery in our hospital during the period from 2006 to 2011. In addition, proteome analysis of liver tumors in male STAM NASH-model mice was performed...
February 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28218435/a-low-frequency-variant-in-smad7-modulates-tgf-%C3%AE-signaling-and-confers-risk-for-colorectal-cancer-in-chinese-population
#8
Jiaoyuan Li, Li Zou, Ying Zhou, Lu Li, Ying Zhu, Yang Yang, Yajie Gong, Jiao Lou, Juntao Ke, Yi Zhang, Jianbo Tian, Danyi Zou, Xiating Peng, Jiang Chang, Jing Gong, Rong Zhong, Xiaobo Zhou, Xiaoping Miao
The TGF-β pathway plays an essential role in regulating cell proliferation and differentiation. GWASs and candidate approaches have identified a battery of genetic variants in the TGF-β pathway contributing to colorectal cancer (CRC). However, most of the significant variants are common variants and their functions remain ambiguous. To identify causal variants with low-frequency in the TGF-β pathway contributing to CRC susceptibility in Chinese population, we performed targeted sequencing of 12 key genes in TGF-β signaling in CRC patients followed by a two-stage case-control study with a total of 5109 cases and 5169 controls...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28217371/pathogenic-mechanisms-of-pancreatitis
#9
REVIEW
Murli Manohar, Alok Kumar Verma, Sathisha Upparahalli Venkateshaiah, Nathan L Sanders, Anil Mishra
Pancreatitis is inflammation of pancreas and caused by a number of factors including pancreatic duct obstruction, alcoholism, and mutation in the cationic trypsinogen gene. Pancreatitis is represented as acute pancreatitis with acute inflammatory responses and; chronic pancreatitis characterized by marked stroma formation with a high number of infiltrating granulocytes (such as neutrophils, eosinophils), monocytes, macrophages and pancreatic stellate cells (PSCs). These inflammatory cells are known to play a central role in initiating and promoting inflammation including pancreatic fibrosis, i...
February 6, 2017: World Journal of Gastrointestinal Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28214372/canonical-and-cellular-pathways-timing-gamete-release-in-acropora-digitifera-okinawa-japan
#10
Y Rosenberg, T Doniger, S Harii, F Sinniger, O Levy
Natural light cycles are important for synchronizing behavioral and physiological rhythms over varying time-periods in both plants and animals. An endogenous clock, regulated by positive and negative elements, interacting in feedback loops, control these rhythms. Many corals exhibit diel cycles of polyp expansion and contraction entrained by solar light patterns and monthly cycles of spawning or planulation that correspond to nocturnal lunar light cycles. However, despite considerable interest in studies of coral reproduction, there is currently not enough molecular information about the cellular pathways involved with synchronizing spawning/planulation in broadcast spawners and brooders...
February 18, 2017: Molecular Ecology
https://www.readbyqxmd.com/read/28213973/transforming-growth-factor-%C3%AE-induces-bone-marrow-mesenchymal-stem-cell-migration-via-noncanonical-signals-and-n-cadherin
#11
Maria Jose Dubon, Jinyeong Yu, Sanghyuk Choi, Ki-Sook Park
Transforming growth factor-beta (TGF-β) induces the migration and mobilization of bone marrow-derived mesenchymal stem cells (BM-MSCs) to maintain bone homeostasis during bone remodeling and facilitate the repair of peripheral tissues. Although many studies have reported the mechanisms through which TGF-β mediates the migration of various types of cells, including cancer cells, the intrinsic cellular mechanisms underlying cellular migration and mobilization of BM-MSCs mediated by TGF-β are unclear. In this study, we showed that TGF-β activated noncanonical signaling molecules, such as Akt, extracellular signal-regulated kinase 1/2 (ERK1/2), focal adhesion kinase (FAK), and p38, via TGF-β type I receptor in human BM-MSCs and murine BM-MSC-like ST2 cells...
February 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28210075/pancreatic-stellate-cell-pandora-s-box-for-pancreatic-disease-biology
#12
REVIEW
Ratnakar R Bynigeri, Aparna Jakkampudi, Ramaiah Jangala, Chivukula Subramanyam, Mitnala Sasikala, G Venkat Rao, D Nageshwar Reddy, Rupjyoti Talukdar
Pancreatic stellate cells (PSCs) were identified in the early 1980s, but received much attention after 1998 when the methods to isolate and culture them from murine and human sources were developed. PSCs contribute to a small proportion of all pancreatic cells under physiological condition, but are essential for maintaining the normal pancreatic architecture. Quiescent PSCs are characterized by the presence of vitamin A laden lipid droplets. Upon PSC activation, these perinuclear lipid droplets disappear from the cytosol, attain a myofibroblast like phenotype and expresses the activation marker, alpha smooth muscle actin...
January 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28209981/fibulin-6-regulates-pro-fibrotic-tgf-%C3%AE-responses-in-neonatal-mouse-ventricular-cardiac-fibroblasts
#13
Arpita Chowdhury, Lisa Hasselbach, Frank Echtermeyer, Nidhi Jyotsana, Gregor Theilmeier, Christine Herzog
Fibulin-6, an essential component of extracellular matrix determines the architecture of cellular junctions in tissues undergoing strain. Increased expression and deposition of fibulin-6 facilitates fibroblast migration in response to TGF-β, following myocardial infarction in mouse heart. The underlying mechanism still remains elusive. In conjunction with our previous study, we have now demonstrated that in fibulin-6 knockdown (KD) fibroblasts, not only TGF-β dependent migration, but also stress fiber formation, cellular networking and subsequently fibroblast wound contraction is almost abrogated...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28208683/plasma-gelsolin-induced-glomerular-fibrosis-via-the-tgf-%C3%AE-1-smads-signal-transduction-pathway-in-iga-nephropathy
#14
Lei Zhang, Changsong Han, Fei Ye, Yan He, Yinji Jin, Tianzhen Wang, Yiqi Wu, Yang Jiang, Fengmin Zhang, Xiaoming Jin
Glomerular fibrosis has been shown to be closely related to the progression and prognosis of IgA nephropathy (IgAN). However, mechanism underlying IgAN glomerular fibrosis remains unclear. Recently, our study showed that plasma gelsolin (pGSN) was decreased in the serum of an IgAN mouse model and that pGSN deposition was found in the glomeruli. Another cytokine, TGF-β1, which is closely related to glomerular fibrosis, was also found to be highly expressed in the glomeruli. In the present study, we report that pGSN induces glomerular fibrosis through the TGF-β1/Smads signal transduction pathway...
February 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28207189/effects-of-human-mesenchymal-stem-cells-co-culture-on-calcium-induced-differentiation-of-normal-human-keratinocytes
#15
Shyam Kishor Sah, Hae Young Kim, Ji Hae Lee, Seong-Wook Lee, Hyung-Sik Kim, Yeon-Soo Kim, Kyung-Sun Kang, Tae-Yoon Kim
The influence of mesenchymal stem cells (MSCs) on keratinocytes in altered microenvironments is poorly understood. Here, we co-cultured umbilical cord blood-derived MSCs with normal human epidermal keratinocytes (NHEK) to evaluate their paracrine effect in the presence of high extracellular calcium (Ca(2+) ) concentration. High Ca(2+) environment to keratinocytes can disrupt normal skin barrier function due to abnormal/premature differentiation of keratinocytes. Surprisingly, we found that MSCs suppress both proliferation and differentiation of keratinocytes under a high Ca(2+) environment in TGFβ1-dependent manner...
February 16, 2017: Stem Cells
https://www.readbyqxmd.com/read/28203261/curcumin-suppresses-intestinal-fibrosis-by-inhibition-of-ppar%C3%AE-mediated-epithelial-mesenchymal-transition
#16
Su Xu, Bin Jiang, Hui Wang, Cunsi Shen, Hao Chen, Li Zeng
Intestinal fibrotic stricture is a major complication of Crohn's disease (CD) and epithelial-to-mesenchymal transition (EMT) is considered as an important contributor to the formation of intestinal fibrosis by increasing extracellular matrix (ECM) proteins. Curcumin, a compound derived from rhizomes of Curcuma, has been demonstrated with a potent antifibrotic effect. However, its effect on intestinal fibrosis and the potential mechanism is not completely understood. Here we found that curcumin pretreatment significantly represses TGF-β1-induced Smad pathway and decreases its downstream α-smooth muscle actin (α-SMA) gene expression in intestinal epithelial cells (IEC-6); in contrast, curcumin increases expression of E-cadherin and peroxisome proliferator-activated receptor γ (PPARγ) in IEC-6...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28202676/harnessing-the-bmp-signaling-pathway-to-control-the-formation-of-cancer-stem-cells-by-effects-on-epithelial-to-mesenchymal-transition
#17
REVIEW
Ashish Bosukonda, William D Carlson
Cancer stem cells (CSCs) persist in tumors as a distinct population and may be causative in metastasis and relapse. CSC-rich tumors are associated with higher rates of metastasis and poor patient prognosis. Targeting CSCs therapeutically is challenging, since they seem to be resistant to standard chemotherapy. We have shown that a novel peptide agonist of bone morphogenetic protein (BMP) signaling, P123, is capable of inhibiting the growth of primary tumor cells by interacting with type I receptors selectively [activin receptor-like kinase 2 (ALK2) and ALK3, but not ALK6] and type II BMP receptors, activating SMAD 1/5/8 signaling and controlling the cell cycle pathway...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28202235/stx12-lncrna-mir-148a-smad5-participate-in-the-regulation-of-pancreatic-stellate-cell-activation-through-a-mechanism-involving-competing-endogenous-rna
#18
Hao Wang, Yanfeng Jiang, Ming Lu, Bei Sun, Xin Qiao, Dongbo Xue, Weihui Zhang
BACKGROUND: With the deepening of research, the roles of LncRNAs play in the fibrotic process have attracted great attention. At the early stage of pancreatic fibrogenesis, to effectively regulate pancreatic stellate cells (PSCs) activation is crucial for the treatment of chronic pancreatic fibrosis. METHODS: Microarray data on chronic pancreatitis were retrieved from the Gene Expression Omnibus (GEO) repository and analyzed using bioinformatic methods. A diagram of the lncRNA-miRNA-mRNA ceRNA network was constructed...
February 1, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/28192879/knockdown-of-irf3-inhibits-extracellular-matrix-expression-in-keloid-fibroblasts
#19
Yi Zhang, Li Zhang, Xiao-Hua Lin, Zhi-Ming Li, Qi-Yu Zhang
Keloid is a pathologic fibro-proliferative disorder and is characterized by hyper-proliferation of fibroblasts and excess extracellular matrix (ECM) deposition. Interferon regulatory factor 3 (IRF3) is a member of the interferon-regulatory factor (IRF) family and has been shown to play a critical modulator in the progression of fibrosis. However, the function of IRF3 in dermal fibrosis remains unclear. Thus, in this study, we investigated the effects of IRF3 on keloid-derived fibroblasts (KFs) proliferation and ECM expression, and explored the underlying mechanism...
February 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28188849/endocytosis-contributes-to-bmp2-induced-smad-signalling-and-neuronal-growth
#20
Shane V Hegarty, Aideen M Sullivan, Gerard W O'Keeffe
Bone morphogenetic protein 2 (BMP2) is a neurotrophic factor which induces the growth of midbrain dopaminergic (DA) neurons in vitro and in vivo, and its neurotrophic effects have been shown to be dependent on activation of BMP receptors (BMPRs) and Smad 1/5/8 signalling. However, the precise intracellular cascades that regulate BMP2-BMPR-Smad-signalling-induced neurite growth remain unknown. Endocytosis has been shown to regulate Smad 1/5/8 signalling and differentiation induced by BMPs. However, these studies were carried out in non-neural cells...
February 8, 2017: Neuroscience Letters
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