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Profibrotic pathways

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https://www.readbyqxmd.com/read/29351440/jq1-is-a-potential-therapeutic-option-for-copd-patients-with-agrin-overexpression
#1
Zhen Xiao, Jing Shu, Feng Zhou, Yong Han
Chronic Obstructive Pulmonary Disease (COPD) is one of the leading cause of morbidity and death worldwide. It is characterized by chronic pulmonary inflammation and obstructed airflow from the lungs. To date, there is no effective treatments for COPD. The activation of Agrin (AGRN) - YAP pathway can promote heart regeneration. Since Agrin can only induce mild cardiomyocyte (CM) proliferation compare to ERBB2 pathway activation, it might exert pleiotropic effects, such as mitigation of innate inflammation, immune response and fibrosis...
December 28, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29343447/altered-b-lymphocyte-homeostasis-and-functions-in-systemic-sclerosis
#2
REVIEW
Alexandra Forestier, Thomas Guerrier, Mathieu Jouvray, Jonathan Giovannelli, Guillaume Lefèvre, Vincent Sobanski, Carine Hauspie, Eric Hachulla, Pierre-Yves Hatron, Hélène Zephir, Patrick Vermersch, Myriam Labalette, David Launay, Sylvain Dubucquoi
Beyond the production of autoantibodies, B-cells are thought to play a role in systemic sclerosis (SSc) by secreting proinflammatory/profibrotic cytokines. B-cells are a heterogeneous population with different subsets distinguished by their phenotypes and cytokine production. Data about B-cell subsets, cytokine production and intracellular pathways leading to this production are scarce in SSc. The aim of our study was to describe B-cell homeostasis, activation, proliferation, cytokine production in B-cells and serum and B-cell intracellular signaling pathways in SSc...
January 14, 2018: Autoimmunity Reviews
https://www.readbyqxmd.com/read/29339038/curcumin-inhibits-tgf-%C3%AE-1-induced-connective-tissue-growth-factor-expression-through-the-interruption-of-smad2-signaling-in-human-gingival-fibroblasts
#3
Jung-Tsu Chen, Chen-Ying Wang, Min-Huey Chen
BACKGROUND/PURPOSE: Many fibrotic processes are associated with an increased level of transforming growth factor-β1 (TGF-β1). TGF-β1 can increase synthesis of matrix proteins and enhance secretion of protease inhibitors, resulting in matrix accumulation. Connective tissue growth factor (CTGF) is a downstream profibrotic effector of TGF-β1 and is associated with the fibrosis in several human organs. Curcumin has been applied to reduce matrix accumulation in fibrotic diseases. This study was aimed to evaluate whether curcumin could suppress TGF-β1-induced CTGF expression and its related signaling pathway involving in this inhibitory action in primary human gingival fibroblasts...
January 13, 2018: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/29321022/serum-metabolic-profiling-identified-a-distinct-metabolic-signature-in-patients-with-idiopathic-pulmonary-fibrosis-a-potential-biomarker-role-for-lysopc
#4
Barbara Rindlisbacher, Cornelia Schmid, Thomas Geiser, Cédric Bovet, Manuela Funke-Chambour
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease of unknown etiology. Patients present loss of lung function, dyspnea and dry cough. Diagnosis requires compatible radiologic imaging and, in undetermined cases, invasive procedures such as bronchoscopy and surgical lung biopsy. The pathophysiological mechanisms of IPF are not completely understood. Lung injury with abnormal alveolar epithelial repair is thought to be a major cause for activation of profibrotic pathways in IPF...
January 10, 2018: Respiratory Research
https://www.readbyqxmd.com/read/29311148/protein-kinases-g-are-essential-downstream-mediators-of-the-antifibrotic-effects-of-sgc-stimulators
#5
Alexandru-Emil Matei, Christian Beyer, Andrea-Hermina Györfi, Alina Soare, Chih-Wei Chen, Clara Dees, Christina Bergmann, Andreas Ramming, Andreas Friebe, Franz Hofmann, Oliver Distler, Georg Schett, Jörg H W Distler
OBJECTIVES: Stimulators of soluble guanylate cyclase (sGC) are currently investigated in clinical trials for the treatment of fibrosis in systemic sclerosis (SSc). In this study, we aim to investigate the role of protein kinases G (PKG) as downstream mediators of sGC-cyclic guanosine monophosphate (cGMP) in SSc. METHODS: Mice with combined knockout of PKG1 and 2 were challenged with bleomycin and treated with the sGC stimulator BAY 41-2272. Fibroblasts were treated with BAY 41-2272 and with the PKG inhibitor KT 5823...
January 8, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29310804/the-cytoskeletal-network-regulates-expression-of-the-profibrotic-genes-pai-1-and-ctgf-in-vascular-smooth-muscle-cells
#6
Rohan Samarakoon, Paul J Higgins
Vascular smooth muscle cells (VSMCs) are subject to changing hemodynamic stimuli that alter cytoskeletal dynamics, cellular architecture, and structure-associated signal transduction. Tensional stress, force application, and structural perturbations are sensed by VSMCs and impact the physiological as well as pathophysiological responses of the vasculature. Microtubule-targeting drugs provide useful tools to analyze cytoskeletal-associated signaling pathways and their linkages to pathological outcomes. Architecture-based controls on a subset of profibrotic genes commonly expressed in vascular disease are highlighted by their frequent induction in mechanically manipulated cells and with associated changes in cytoskeletal dynamics...
2018: Advances in Pharmacology
https://www.readbyqxmd.com/read/29287092/connective-tissue-growth-factor-dependent-collagen-gene-expression-induced-by-mas-agonist-ar234960-in-human-cardiac-fibroblasts
#7
Arunachal Chatterjee, John Barnard, Christine Moravec, Russell Desnoyer, Kalyan Tirupula, Sadashiva S Karnik
Perspectives on whether the functions of MAS, a G protein-coupled receptor, are beneficial or deleterious in the heart remain controversial. MAS gene knockout reduces coronary vasodilatation leading to ischemic injury. G protein signaling activated by MAS has been implicated in progression of adaptive cardiac hypertrophy to heart failure and fibrosis. In the present study, we observed increased expression of MAS, connective tissue growth factor (CTGF) and collagen genes in failing (HF) human heart samples when compared to non-failing (NF)...
2017: PloS One
https://www.readbyqxmd.com/read/29277328/induction-of-cytochrome-p450-4a14-contributes-to-angiotensin-ii-induced-renal-fibrosis-in-mice
#8
Yunfeng Zhou, Jingwei Yu, Jia Liu, Rong Cao, Wen Su, Sha Li, Shiqi Ye, Chenggang Zhu, Xiaolin Zhang, Hu Xu, Hua Chen, Xiaoyan Zhang, Youfei Guan
Angiotensin II (AngII) plays an important role in the pathogenesis of hypertension and associated renal injuries. To elucidate the molecular mechanism by which AngII induces renal damage, we found that AngII infusion significantly induced CYP4A14 expression in renal proximal tubule cells (RPTCs) with marked increases in blood pressure and proteinuria. Renal production of the major CYP4A metabolite, 20-HETE, was also significantly increased in the AngII-treated mice. Compared to wild-type (WT) mice, CYP4A14 knockout (CYP4A14-/-) mice exhibited significantly lower levels of blood pressure, renal 20-HETE production, proteinuria and renal fibrosis following AngII infusion...
December 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29215326/the-role-of-fabp5-in-radiation-induced-human-skin-fibrosis
#9
Jianyuan Song, Huojun Zhang, Zhenyu Wang, Wanglei Xu, Li Zhong, Jinming Cao, Jianfeng Yang, Ye Tian, Daojiang Yu, Jiang Ji, Jianping Cao, Shuyu Zhang
Radiation-induced skin fibrosis is a detrimental and chronic disorder that occurs after radiation exposure. The molecular changes underlying the pathogenesis of radiation-induced fibrosis of human skin have not been extensively reported. Technical advances in proteomics have enabled exploration of the biomarkers and molecular pathogenesis of radiation-induced skin fibrosis, with the potential to broaden our understanding of this disease. In this study, we compared protein expression in radiation-induced fibrotic human skin and adjacent normal tissues using iTRAQ-based proteomics technology...
December 7, 2017: Radiation Research
https://www.readbyqxmd.com/read/29214163/protective-effects-of-pyridoxamine-supplementation-in-the-early-stages-of-diet-induced-kidney-dysfunction
#10
F Chiazza, A S Cento, D Collotta, D Nigro, G Rosa, F Baratta, V Bitonto, J C Cutrin, M Aragno, R Mastrocola, M Collino
Pyridoxamine, a structural analog of vitamin B6 that exerts antiglycative effects, has been proposed as supplementary approach in patients with initial diabetic nephropathy. However, the molecular mechanism(s) underlying its protective role has been so far slightly examined. C57Bl/6J mice were fed with a standard diet (SD) or a diet enriched in fat and fructose (HD) for 12 weeks. After 3 weeks, two subgroups of SD and HD mice started pyridoxamine supplementation (150 mg/kg/day) in the drinking water. HD fed mice showed increased body weight and impaired glucose tolerance, whereas pyridoxamine administration significantly improved insulin sensitivity, but not body weight, and reduced diet-induced increase in serum creatinine and urine albumin...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29193875/dabigatran-inhibits-intravitreal-thrombin-activity
#11
Jeroen Bastiaans, Verena C Mulder, Jan C van Meurs, Marja Smits-Te Nijenhuis, Conny van Holten-Neelen, P Martin van Hagen, Willem A Dik
PURPOSE: Proliferative vitreoretinopathy (PVR) is a vitreoretinal disorder in which retinal pigment epithelial (RPE) cell activation contributes to both formation of fibrotic retinal membranes and inflammation. Vitreous of patients with PVR contains increased thrombin activity which induces profibrotic and proinflammatory programs in RPE cells. Inhibition of intravitreal thrombin activity may thus represent a therapeutic option for PVR. In this study, we examined the capacity of the clinically available direct thrombin inhibitor dabigatran to inhibit thrombin activity in vitreous fluids...
November 30, 2017: Acta Ophthalmologica
https://www.readbyqxmd.com/read/29191563/tgf-%C3%AE-1-p53-signaling-in-renal-fibrogenesis
#12
Stephen P Higgins, Yi Tang, Craig E Higgins, Badar Mian, Wenzheng Zhang, Ralf-Peter Czekay, Rohan Samarakoon, David J Conti, Paul J Higgins
Fibrotic disorders of the renal, pulmonary, cardiac, and hepatic systems are associated with significant morbidity and mortality. Effective therapies to prevent or curtail the advancement to organ failure, however, remain a major clinical challenge. Chronic kidney disease, in particular, constitutes an increasing medical burden affecting >15% of the US population. Regardless of etiology (diabetes, hypertension, ischemia, acute injury, urologic obstruction), persistently elevated TGF-β1 levels are causatively linked to the activation of profibrotic signaling networks and disease progression...
November 28, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29186429/extracellular-matrix-in-uterine-leiomyoma-pathogenesis-a-potential-target-for-future-therapeutics
#13
Md Soriful Islam, Andrea Ciavattini, Felice Petraglia, Mario Castellucci, Pasquapina Ciarmela
BACKGROUND: Uterine leiomyoma (also known as fibroid or myoma) is the most common benign tumor of the uterus found in women of reproductive age. It is not usually fatal but can produce serious clinical symptoms, including excessive uterine bleeding, pelvic pain or pressure, infertility and pregnancy complications. Due to lack of effective medical treatments surgery has been a definitive choice for the management of this tumor. OBJECTIVE AND RATIONALE: Extracellular matrix (ECM) accumulation and remodeling are thought to be crucial for fibrotic diseases such as uterine leiomyoma...
January 1, 2018: Human Reproduction Update
https://www.readbyqxmd.com/read/29160908/connective-tissue-growth-factor-induces-renal-fibrosis-via-epidermal-growth-factor-receptor-activation
#14
Sandra Rayego-Mateos, José Luis Morgado-Pascual, Raúl R Rodrigues-Diez, Raquel Rodrigues-Diez, Lucas Falke, Sergio Mezzano, Alberto Ortiz, Jesús Egido, Roel Goldschmeding, Marta Ruiz-Ortega
Connective tissue growth factor (CCN2/CTGF) is a matricellular protein overexpressed in progressive human renal diseases, mainly in fibrotic areas. In vitro studies have demonstrated that CCN2 regulates production of extracellular matrix (ECM) proteins and epithelial mesenchymal transition (EMT), and therefore could contribute to renal fibrosis. CCN2 blockade ameliorates experimental renal damage, including diminution of ECM accumulation. We have described that CCN2 and its C-terminal degradation product CCN2(IV), bind to epidermal growth factor receptor (EGFR) to modulate renal inflammation...
November 21, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29115435/human-umbilical-cord-mesenchymal-stem-cells-alleviate-interstitial-fibrosis-and-cardiac-dysfunction-in-a-dilated-cardiomyopathy-rat-model-by-inhibiting-tnf%C3%A2-%C3%AE-and-tgf%C3%A2-%C3%AE-1-erk1-2-signaling-pathways
#15
Changyi Zhang, Guichi Zhou, Yezeng Chen, Sizheng Liu, Fen Chen, Lichun Xie, Wei Wang, Yonggang Zhang, Tianyou Wang, Xiulan Lai, Lian Ma
Dilated cardiomyopathy (DCM) is a disease of the heart characterized by pathological remodeling, including patchy interstitial fibrosis and degeneration of cardiomyocytes. In the present study, the beneficial role of human umbilical cord‑derived mesenchymal stem cells (HuMSCs) derived from Wharton's jelly was evaluated in the myosin‑induced rat model of DCM. Male Lewis rats (aged 8‑weeks) were injected with porcine myosin to induce DCM. Cultured HuMSCs (1x106 cells/rat) were intravenously injected 28 days after myosin injection and the effects on myocardial fibrosis and the underlying signaling pathways were investigated and compared with vehicle‑injected and negative control rats...
October 26, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29111086/role-of-interleukin-17-in-tgf-%C3%AE-signaling-mediated-renal-interstitial-fibrosis
#16
Bin Sun, Hui Wang, Lu Zhang, Xiaofan Yang, Mingshun Zhang, Xingxing Zhu, Xiaohui Ji, Huijuan Wang
BACKGROUND: Several studies suggest IL-17 is involved in the pathogenesis of organ fibrosis. The exact role of IL-17 in renal interstitial fibrosis has not been fully elucidated. METHODS: We compared the histopathology of renal fibrosis as well as profibrotic TGF-β signaling in wild-type (WT) and IL-17 knock-out (IL-17(-/-)) mice using UUO as the disease model. To find out the possible mechanisms involved in the exacerbated renal fibrosis happened to IL-17(-/-) mice, we analyzed the pattern of ECM synthesis by different fibroblasts cultured with IL-17 and associated signaling mediators...
October 27, 2017: Cytokine
https://www.readbyqxmd.com/read/29101170/the-prorenin-receptor-in-the-cardiovascular-system-and-beyond
#17
Matthew T Hennrikus, Alexis A Gonzalez, Minolfa C Prieto
Since the prorenin receptor (PRR) was first reported, investigations into its role in many cellular processes have been underway. Renin and prorenin binding to PRR and its soluble form (sPRR) increases angiotensin I formation and intracellular pathways resulting in induction of profibrotic factors. The PRR has supplementary roles as a vital accessory protein of the vacuolar-type H+-ATPase and also as an intermediate in Wnt signaling. As a component of the H-ATPase, the PRR has been found upregulated during cardiac stress...
November 3, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29093267/loss-of-mir-141-200c-ameliorates-hepatic-steatosis-and-inflammation-by-reprogramming-multiple-signaling-pathways-in-nash
#18
Melanie Tran, Sang-Min Lee, Dong-Ju Shin, Li Wang
Accumulation of lipid droplets and inflammatory cell infiltration is the hallmark of nonalcoholic steatohepatitis (NASH). The roles of noncoding RNAs in NASH are less known. We aim to elucidate the function of miR-141/200c in diet-induced NASH. WT and miR-141/200c-/- mice were fed a methionine and choline deficient (MCD) diet for 2 weeks to assess markers of steatosis, liver injury, and inflammation. Hepatic miR-141 and miR-200c RNA levels were highly induced in human patients with NASH fatty liver and in WT MCD mice...
November 2, 2017: JCI Insight
https://www.readbyqxmd.com/read/29080401/reactive-oxygen-species-as-signaling-molecules-in-the-development-of-lung-fibrosis
#19
REVIEW
Francisco J Gonzalez-Gonzalez, Navdeep Chandel, Manu Jain, G R Scott Budinger
Pulmonary fibrosis is a relatively rare but devastating disease characterized by the excessive deposition of extracellular matrix. The increased matrix results in reduced lung compliance and increased work of breathing, while the obliteration of alveolar-capillary structures can result in hypoxemia and pulmonary hypertension, which manifests clinically as worsening shortness of breath, respiratory failure, and death. Unbiased genome-wide association studies combined with animal models suggest that damage to the alveolar epithelium is the initiating factor in pulmonary fibrosis...
October 10, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29073967/inhibition-of-glycogen-synthase-kinase-3%C3%AE-blocks-mesomesenchymal-transition-and-attenuates-streptococcus-pneumonia-mediated-pleural-injury-in-mice
#20
Jake Boren, Grant Shryock, Alexis Fergis, Ann Jeffers, Shuzi Owens, Wenyi Qin, Kathleen B Koenig, Yoshikazu Tsukasaki, Satoshi Komatsu, Mitsuo Ikebe, Steven Idell, Torry A Tucker
Pleural loculation affects about 30,000 patients annually in the United States and in severe cases can resolve with restrictive lung disease and pleural fibrosis. Pleural mesothelial cells contribute to pleural rind formation by undergoing mesothelial mesenchymal transition (MesoMT), whereby they acquire a profibrotic phenotype characterized by increased expression of α-smooth muscle actin and collagen 1. Components of the fibrinolytic pathway (urokinase plasminogen activator and plasmin) are elaborated in pleural injury and strongly induce MesoMT in vitro...
November 2017: American Journal of Pathology
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