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Profibrotic pathways

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https://www.readbyqxmd.com/read/29768198/myocardin-related-transcription-factor-a-promotes-recruitment-of-itga5-profibrotic-progenitors-during-obesity-induced-adipose-tissue-fibrosis
#1
Jean Z Lin, Nabil Rabhi, Stephen R Farmer
Adipose tissue fibrosis is associated with inflammation and insulin resistance in human obesity. In particular, visceral fat fibrosis is correlated with hyperlipidemia and ectopic fat accumulation. Myocardin-related transcription factor A (MRTFA) is an important coactivator that mediates the transcription of extracellular matrix and other fibrogenic genes. Here, we examine the role of MRTFA in the development of adipose tissue fibrosis and identify a signaling pathway that regulates the fate of vascular progenitors...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29765500/mito-tempo-alleviates-renal-fibrosis-by-reducing-inflammation-mitochondrial-dysfunction-and-endoplasmic-reticulum-stress
#2
Yuqing Liu, Yundan Wang, Wei Ding, Yingdeng Wang
Background: Renal fibrosis is a common pathological symptom of chronic kidney disease (CKD). Many studies support that mitochondrial dysfunction and endoplasmic reticulum (ER) stress are implicated in the pathogenesis of CKD. In our study, we investigated the benefits and underlying mechanisms of Mito-TEMPO on renal fibrosis in 5/6 nephrectomy mice. Methods: Mice were randomly divided into five groups as follows: control group, CKD group, CKD + Mito-TEMPO (1 mg·kg-1 ·day-1 ) group, CKD + Mito-TEMPO (3 mg·kg-1 ·day-1 ) group, and Mito-TEMPO group (3 mg·kg-1 ·day-1 )...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29749461/upregulation-of-allograft-inflammatory-factor%C3%A2-1-expression-and-secretion-by-macrophages-stimulated-with-aldosterone-promotes-renal-fibroblasts-to-a-profibrotic-phenotype
#3
Yushu Li, Xingzhi Wang, Lei Zhang, Xueying Yuan, Jianbing Hao, Jie Ni, Lirong Hao
Macrophages have been identified as a key cell type in the pathogenesis of renal interstitial fibrosis (RIF). However, the mechanism through which macrophages drive fibrosis remains unclear. The current study focuses on the effects and possible underlying mechanism of allograft inflammatory factor‑1 (AIF‑1), an inflammation‑responsive scaffold protein expressed and secreted by macrophages, in promoting fibroblasts to a profibrotic phenotype. In vivo experiments indicated that AIF‑1, CD68 and α‑smooth muscle actin (α‑SMA) were upregulated in kidney tissues of mice subjected to unilateral ureteric obstruction, while their expressions were inhibited by an aldosterone receptor antagonist, spironolactone...
May 10, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29743985/andrographolide-ameliorates-liver-fibrosis-in-mice-involvement-of-tlr4-nf-%C3%AE%C2%BA-b-and-tgf-%C3%AE-1-smad2-signaling-pathways
#4
Liteng Lin, Rui Li, Mingyue Cai, Jingjun Huang, Wensou Huang, Yongjian Guo, Liuhong Yang, Guizhi Yang, Tian Lan, Kangshun Zhu
Liver fibrosis is characterized by activated hepatic stellate cells (HSC) and extracellular matrix accumulation. Blocking the activation of HSC and the inflammation response are two major effective therapeutic strategies for liver fibrosis. In addition to the long history of using andrographolide (Andro) for inflammatory disorders, we aimed at elucidating the pharmacological effects and potential mechanism of Andro on liver fibrosis. In this study, liver fibrosis was induced by carbon tetrachloride (CCl4 ) and the mice were intraperitoneally injected with Andro for 6 weeks...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29679710/cpg-oligodeoxynucleotides-may-be-effective-for-preventing-ionizing-radiation-induced-pulmonary-fibrosis
#5
Chao Zhang, Hainan Zhao, Bai-Long Li, Fu-Gao, Hu Liu, Jian-Ming Cai
Pulmonary fibrosis is a serious adverse effect of radiotherapy for thoracic tumor, which is believed to be a process that is tightly regulated by the phenotype of the developing Th response after radiation. Here, we will investigate whether CpG-oligodeoxynucleotides (ODN) prevent radiation-induced pulmonary fibrosis by shifting the imbalance of Th1 and Th2 response and summarizes the possible mechanism. In this study, female C57BL/6 mice were chosen to preform pulmonary fibrosis model, the whole-thorax of mice was exposed to a single radiation dose of 15 Gy...
April 18, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29668883/deletion-of-delta-like-1-homologue-accelerates-fibroblast-myofibroblast-differentiation-and-induces-myocardial-fibrosis
#6
Patricia Rodriguez, Yassine Sassi, Luca Troncone, Ludovic Benard, Kiyotake Ishikawa, Ronald E Gordon, Santiago Lamas, Jorge Laborda, Roger J Hajjar, Djamel Lebeche
Aims: Myocardial fibrosis is associated with profound changes in ventricular architecture and geometry, resulting in diminished cardiac function. There is currently no information on the role of the delta-like homologue 1 (Dlk1) in the regulation of the fibrotic response. Here, we investigated whether Dlk1 is involved in cardiac fibroblast-to-myofibroblast differentiation and regulates myocardial fibrosis and explored the molecular mechanism underpinning its effects in this process. Methods and results: Using Dlk1-knockout mice and adenoviral gene delivery, we demonstrate that overexpression of Dlk1 in cardio-fibroblasts resulted in inhibition of fibroblast proliferation and differentiation into myofibroblasts...
April 13, 2018: European Heart Journal
https://www.readbyqxmd.com/read/29656123/selenium-supplementation-prevents-metabolic-and-transcriptomic-responses-to-cadmium-in-mouse-lung
#7
Xin Hu, Joshua D Chandler, Jolyn Fernandes, Michael L Orr, Li Hao, Karan Uppal, David C Neujahr, Dean P Jones, Young-Mi Go
BACKGROUND: The protective effect of selenium (Se) on cadmium (Cd) toxicity is well documented, but underlying mechanisms are unclear. METHODS: Male mice fed standard diet were given Cd (CdCl2 , 18 μmol/L) in drinking water with or without Se (Na2 SeO4, 20 μmol/L) for 16 weeks. Lungs were analyzed for Cd concentration, transcriptomics and metabolomics. Data were analyzed with biostatistics, bioinformatics, pathway enrichment analysis, and combined transcriptome-metabolome-wide association study...
April 12, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29625182/idiopathic-pulmonary-fibrosis-epithelial-mesenchymal-interactions-and-emerging-therapeutic-targets
#8
REVIEW
Justin C Hewlett, Jonathan A Kropski, Timothy S Blackwell
Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic disease of the lung that is marked by progressive decline in pulmonary function and ultimately respiratory failure. Genetic and environmental risk factors have been identified that indicate injury to, and dysfunction of the lung epithelium is central to initiating the pathogenic process. Following injury to the lung epithelium, growth factors, matrikines and extracellular matrix driven signaling together activate a variety of repair pathways that lead to inflammatory cell recruitment, fibroblast proliferation and expansion of the extracellular matrix, culminating in tissue fibrosis...
April 3, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29599211/experimental-right-ventricular-hypertension-induces-regional-%C3%AE-1-integrin-mediated-transduction-of-hypertrophic-and-profibrotic-right-and-left-ventricular-signaling
#9
Mei Sun, Ryo Ishii, Kenichi Okumura, Adrienn Krauszman, Siegfried Breitling, Olga Gomez, Aleksander Hinek, Stellar Boo, Boris Hinz, Kim A Connelly, Wolfgang M Kuebler, Mark K Friedberg
BACKGROUND: Development of right ventricular (RV) hypertension eventually contributes to RV and left ventricular (LV) myocardial fibrosis and dysfunction. The molecular mechanisms are not fully elucidated. METHODS AND RESULTS: Pulmonary artery banding was used to induce RV hypertension in rats in vivo. Then, we evaluated cardiac function and regional remodeling 6 weeks after pulmonary artery banding. To further elucidate mechanisms responsible for regional cardiac remodeling, we also mimicked RV hypertensive stress by cyclic mechanical stretching applied to confluent cultures of cardiac fibroblasts, isolated from the RV free wall, septal hinge points, and LV free wall...
March 29, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29563334/allele-specific-differences-in-transcriptome-mirnome-and-mitochondrial-function-in-two-hypertrophic-cardiomyopathy-mouse-models
#10
Styliani Vakrou, Ryuya Fukunaga, D Brian Foster, Lars Sorensen, Yamin Liu, Yufan Guan, Kirubel Woldemichael, Roberto Pineda-Reyes, Ting Liu, Jill C Tardiff, Leslie A Leinwand, Carlo G Tocchetti, Theodore P Abraham, Brian O'Rourke, Miguel A Aon, M Roselle Abraham
Hypertrophic cardiomyopathy (HCM) stems from mutations in sarcomeric proteins that elicit distinct biophysical sequelae, which in turn may yield radically different intracellular signaling and molecular pathologic profiles. These signaling events remain largely unaddressed by clinical trials that have selected patients based on clinical HCM diagnosis, irrespective of genotype. In this study, we determined how two mouse models of HCM differ, with respect to cellular/mitochondrial function and molecular biosignatures, at an early stage of disease...
March 22, 2018: JCI Insight
https://www.readbyqxmd.com/read/29557906/autocrine-activation-of-fibroblasts-by-induction-of-il-11-expression-is-a-common-pathway-of-profibrotic-factors
#11
Matthias Mack
No abstract text is available yet for this article.
March 20, 2018: Transplantation
https://www.readbyqxmd.com/read/29525327/obesity-related-heart-failure-with-a-preserved-ejection-fraction-the-mechanistic-rationale-for-combining-inhibitors-of-aldosterone-neprilysin-and-sodium-glucose-cotransporter-2
#12
REVIEW
Milton Packer, Dalane W Kitzman
Obesity-related heart failure with a preserved ejection fraction (HFpEF) is an important phenotype prevalent in the community, especially in people with metabolic disorders (e.g., dyslipidemia, diabetes). These individuals exhibit a marked expansion of plasma volume, but ventricular distensibility is limited, most likely as a result of cardiac microvascular rarefaction acting in concert with myocardial and pericardial fibrosis. Consequently, the increase in plasma volume causes a disproportionate increase in cardiac filling pressures, leading to heart failure, even though systolic ejection is not impaired...
March 7, 2018: JACC. Heart Failure
https://www.readbyqxmd.com/read/29518614/central-role-of-dysregulation-of-tgf-%C3%AE-smad-in-ckd-progression-and-potential-targets-of-its-treatment
#13
REVIEW
Lin Chen, Tian Yang, De-Wen Lu, Hui Zhao, Ya-Long Feng, Hua Chen, Dan-Qian Chen, Nosratola D Vaziri, Ying-Yong Zhao
Chronic kidney disease (CKD) has emerged as a major cause of morbidity and mortality worldwide. Interstitial fibrosis, glomerulosclerosis and inflammation play the central role in the pathogenesis and progression of CKD to end stage renal disease (ESRD). Transforming growth factor-β1 (TGF-β1) is the central mediator of renal fibrosis and numerous studies have focused on inhibition of TGF-β1 and its downstream targets for treatment of kidney disease. However, blockade of TGF-β1 has not been effective in the treatment of CKD patients...
May 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29506624/ccn3-a-key-matricellular-protein-distinctly-inhibits-tgf%C3%AE-1-mediated-smad1-5-8-signalling-in-human-podocyte-culture
#14
Tarunkumar Hemraj Madne, Mark Edward Carl Dockrell
Growth factors like TGFβ and CTGF (CCN2) plays a vital role in various cellular functions. TGFβ and CTGF are overexpressed in renal fibrosis. CTGF act as profibrotic stimuli to TGFβ. CCN3 is a member of CCN family which also comprises CCN1 (CYR61), CCN2 (CTGF), CCN4 (WISP-1), CCN5 (WISP-2) and CCN6 (WISP-3). CCN3 has been shown to antagonise CTGF. In this study, we investigated the role of CCN3 in TGFβ1-mediated signalling in human podocytes culture. This study describes the novel function of CCN3 in regulation of TGFβ1 mediated non-canonical Smad signalling in human podocytes culture...
February 28, 2018: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/29500512/mesenchymal-stem-cells-inhibit-hypoxia-induced-inflammatory-and-fibrotic-pathways-in-bladder-smooth-muscle-cells
#15
Bridget Wiafe, Adetola Adesida, Thomas Churchill, Peter Metcalfe
PURPOSE: Partial bladder outlet obstruction is a multifactorial urological condition in which hypoxia plays a significant role. We recently investigated hypoxia's role as a single stressor and found that hypoxia induced an intense inflammatory and profibrotic switch in bladder smooth muscle cells (bSMCs). With the immunomodulatory capacity of mesenchymal stem cells (MSCs), we aimed to investigate if the hypoxia-signaling pathways can be mitigated using MSCs. METHODS: Bladder smooth muscle cells were cultured in 3% oxygen tension for 72 h with either the direct or indirect co-culture with bone marrow derived MSCs...
March 2, 2018: World Journal of Urology
https://www.readbyqxmd.com/read/29497173/pirfenidone-reduces-profibrotic-responses-in-human-dermal-myofibroblasts-in-vitro
#16
Caroline L Hall, Adrienne R Wells, Kai P Leung
Pirfenidone (PFD) is a synthetic small molecule inhibitor with demonstrated anti-inflammatory and antifibrotic properties in vitro and in vivo. The exact mechanism(s) of PFD action remain unclear, due in part to the broad effects of this drug on the complex processes involved in inflammation and fibrosis. While PFD is FDA-approved for the treatment of idiopathic pulmonary fibrosis, the efficacy of this compound for the treatment of dermal fibrosis has not yet been fully characterized. Dermal fibrosis is the pathological formation of excess fibrous connective tissue of the skin, usually the result of traumatic cutaneous injury...
March 1, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29490938/lipoxins-regulate-the-early-growth-response-1-network-and-reverse-diabetic-kidney-disease
#17
Eoin P Brennan, Muthukumar Mohan, Aaron McClelland, Christos Tikellis, Mark Ziemann, Antony Kaspi, Stephen P Gray, Raelene Pickering, Sih Min Tan, Syed Tasadaque Ali-Shah, Patrick J Guiry, Assam El-Osta, Karin Jandeleit-Dahm, Mark E Cooper, Catherine Godson, Phillip Kantharidis
Background The failure of spontaneous resolution underlies chronic inflammatory conditions, including microvascular complications of diabetes such as diabetic kidney disease. The identification of endogenously generated molecules that promote the physiologic resolution of inflammation suggests that these bioactions may have therapeutic potential in the context of chronic inflammation. Lipoxins (LXs) are lipid mediators that promote the resolution of inflammation. Methods We investigated the potential of LXA4 and a synthetic LX analog (Benzo-LXA4 ) as therapeutics in a murine model of diabetic kidney disease, ApoE-/- mice treated with streptozotocin...
May 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29485009/oral-submucous-fibrosis-as-an-overhealing-wound-implications-in-malignant-transformation
#18
Mohit Sharma, Smitha Sammith Shetty, Raghu Radhakrishnan
BACKGROUND: Oral submucous fibrosis is an oral potentially malignant disorder with high incidence of malignant transformation and rising global prevalence. However, the genesis of oral submucous fibrosis is still unclear despite superfluity of literature. In the background of ineffective treatment, it is necessary to decode its onset and progression before designing customized treatment regimens. OBJECTIVE: The objective of this article is to decipher the pathogenesis of oral submucous fibrosis in order to identify novel drug targets...
February 26, 2018: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/29481398/%C3%AE-catenin-dependent-wnt-signaling-a-pathway-in-acute-cutaneous-wounding
#19
Antoine L Carre, Michael S Hu, Aaron W James, Kenichiro Kawai, Michael G Galvez, Michael T Longaker, H Peter Lorenz
BACKGROUND: Acute wound healing is a dynamic process that results in the formation of scar tissue. The mechanisms of this process are not well understood; numerous signaling pathways are thought to play a major role. Here, the authors have identified β-catenin-dependent Wnt signaling as an early acute-phase reactant in acute wound healing and scar formation. METHODS: The authors created 6-mm full-thickness excisional cutaneous wounds on adult β-catenin-dependent Wnt signal (BAT-gal) reporter mice...
March 2018: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/29438665/cartilage-intermediate-layer-protein-1-alleviates-pressure-overload-induced-cardiac-fibrosis-via-interfering-tgf-%C3%AE-1-signaling
#20
Cheng-Lin Zhang, Qian Zhao, Hui Liang, Xue Qiao, Jin-Yu Wang, Dan Wu, Li-Ling Wu, Li Li
Cardiac fibrosis is characterized by excessive deposition of extracellular matrix (ECM) proteins in the myocardium and results in decreased ventricular compliance and diastolic dysfunction. Cartilage intermediate layer protein-1 (CILP-1), a novel identified cardiac matricellular protein, is upregulated in most conditions associated with cardiac remodeling, however, whether CILP-1 is involved in pressure overload-induced fibrotic response is unknown. Here, we investigated whether CILP-1 was critically involved in the fibrotic remodeling induced by pressure overload...
March 2018: Journal of Molecular and Cellular Cardiology
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