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Profibrotic pathways

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https://www.readbyqxmd.com/read/27927780/genomic-analysis-of-kidney-allograft-injury-identifies-hematopoietic-cell-kinase-as-a-key-driver-of-renal-fibrosis
#1
Chengguo Wei, Li Li, Madhav C Menon, Weijia Zhang, Jia Fu, Brian Kidd, Karen L Keung, Christopher Woytovich, Ilana Greene, Wenzhen Xiao, Fadi Salem, Zhengzi Yi, John Cijiang He, Joel T Dudley, Barbara Murphy
Renal fibrosis is the common pathway of progression for patients with CKD and chronic renal allograft injury (CAI), but the underlying mechanisms remain obscure. We performed a meta-analysis in human kidney biopsy specimens with CAI, incorporating data available publicly and from our Genomics of Chronic Renal Allograft Rejection study. We identified an Src family tyrosine kinase, hematopoietic cell kinase (Hck), as upregulated in allografts in CAI. Querying the Kinase Inhibitor Resource database revealed that dasatinib, a Food and Drug Administration-approved drug, potently binds Hck with high selectivity...
December 7, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27927603/lysophosphatidic-acid-signaling-through-its-receptor-initiates-profibrotic-epithelial-cell-fibroblast-communication-mediated-by-epithelial-cell-derived-connective-tissue-growth-factor
#2
Norihiko Sakai, Jerold Chun, Jeremy S Duffield, David Lagares, Takashi Wada, Andrew D Luster, Andrew M Tager
The expansion of the fibroblast pool is a critical step in organ fibrosis, but the mechanisms driving expansion remain to be fully clarified. We previously showed that lysophosphatidic acid (LPA) signaling through its receptor LPA1 expressed on fibroblasts directly induces the recruitment of these cells. Here we tested whether LPA-LPA1 signaling drives fibroblast proliferation and activation during the development of renal fibrosis. LPA1-deficient (LPA1(-/-)) or -sufficient (LPA1(+/+)) mice were crossed to mice with green fluorescent protein expression (GFP) driven by the type I procollagen promoter (Col-GFP) to identify fibroblasts...
December 4, 2016: Kidney International
https://www.readbyqxmd.com/read/27894300/pleural-inhibition-of-the-caspase-1-il-1%C3%AE-pathway-diminishes-profibrotic-lung-toxicity-of-bleomycin
#3
Olivier Burgy, Pierre-Simon Bellaye, Sebastien Causse, Guillaume Beltramo, Guillaume Wettstein, Pierre-Marie Boutanquoi, Françoise Goirand, Carmen Garrido, Philippe Bonniaud
BACKGROUND: Idiopathic and toxic pulmonary fibrosis are severe diseases starting classically in the subpleural area of the lung. It has recently been suggested that pleural mesothelial cells acquire a myofibroblast phenotype under fibrotic conditions induced by TGF-β1 or bleomycin. The importance and role of inflammation in fibrogenesis are still controversial. In this work, we explored the role of IL-1β/caspase-1 signaling in bleomycin lung toxicity and in pleural mesothelial cell transformation...
November 29, 2016: Respiratory Research
https://www.readbyqxmd.com/read/27842700/the-aryl-hydrocarbon-receptor-and-its-ligands-inhibit-myofibroblast-formation-and-activation-implications-for-thyroid-eye-disease
#4
Collynn F Woeller, Elisa Roztocil, Christine L Hammond, Steven E Feldon, Richard P Phipps
Thyroid eye disease (TED) is a degenerative disease that manifests with detrimental tissue remodeling, myofibroblast accumulation, and scarring in the orbit of affected individuals. Currently, there are no effective therapies for TED that target or prevent the excessive tissue remodeling caused by myofibroblast formation and activation. The canonical cytokine that induces myofibroblast formation is transforming growth factor (TGF)-β. The TGF-β signaling pathway is influenced by aryl hydrocarbon receptor (AHR) signaling pathways...
November 9, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27784018/the-potential-of-sgc-modulators-for-the-treatment-of-age-related-fibrosis-a-mini-review
#5
Peter Sandner, Peter Berger, Christoph Zenzmaier
Fibrotic diseases cause high rates of morbidity and mortality, and their incidence increases with age. Despite intense research and development efforts, effective and well-tolerated antifibrotic treatments are scarce. Transforming growth factor-β signaling, which is widely considered the most important profibrotic factor, causes a pro-oxidant shift in redox homeostasis and a concomitant decrease in nitric oxide (NO) signaling. The NO/cyclic guanosine monophosphate (cGMP) signaling cascade plays a pivotal role in the regulation of cell and organ function in whole-body hemostasis...
October 27, 2016: Gerontology
https://www.readbyqxmd.com/read/27776513/the-antifibrotic-and-fibrolytic-properties-of-date-fruit-extract-via-modulation-of-genotoxicity-tissue-inhibitor-of-metalloproteinases-and-nuclear-factor-kappa-b-pathway-in-a-rat-model-of-hepatotoxicity
#6
Hala Attia, Nouf Al-Rasheed, Raeesa Mohamad, Nawal Al-Rasheed, Maha Al-Amin
BACKGROUND: Hepatic fibrosis and its end point; cirrhosis, are the major cause of liver failure and death in patients with chronic liver disease. Therefore, the need for an effective treatment is evident. This study was designed to assess the potential effects of aqueous extract of date fruits, either flesh (DFE) or pits (DPE), on oxidative DNA damage and liver inflammation induced by carbon tetrachloride (CCl4) and whether they are related to inhibition of nuclear factor-κB pathway...
October 24, 2016: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/27769060/mir-185-akt-and-mir-29a-collagen-1a-pathways-are-activated-in-ipf-bal-cells
#7
Eliza Tsitoura, Athol U Wells, Kostantinos Karagiannis, Ismini Lasithiotaki, Eirini Vasarmidi, Eleni Bibaki, Chara Koutoulaki, Hiroe Sato, Demetrios A Spandidos, Nikolaos M Siafakas, George Sourvinos, Katerina M Antoniou
MicroRNA signatures of BAL cells and alveolar macrophages are currently lacking in IPF. Here we sought to investigate the expression of fibrosis-related microRNAs in the cellular component of the BAL in IPF. We thus focused on microRNAs previously associated with fibrosis (miR-29a, miR-29b, miR-29c, let-7d, and miR-21) and rapid IPF progression (miR-185, miR-210, miR-302c-3p miR-376c and miR-423-5p). Among the tested microRNAs miR-29a and miR-185 were found significantly downregulated in IPF while miR-302c-3p and miR-376c were not expressed by BAL cells...
October 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27759853/profibrotic-pathways-and-atrial-cardiomyopathy-in-persistent-atrial-fibrillation
#8
Uğur Canpolat
No abstract text is available yet for this article.
October 1, 2016: Clinics
https://www.readbyqxmd.com/read/27736153/sh2-domain-containing-phosphatase-shp-2-is-a-novel-anti-fibrotic-regulator-in-pulmonary-fibrosis
#9
Argyrios Tzouvelekis, Guoying Yu, Christian Lacks Lino Cardenas, Jose D Herazo-Maya, Rong Wang, Tony Woolard, Yi Zhang, Koji Sakamoto, Hojin Lee, Jae-Sung Yi, Giuseppe DeIuliis, Nikolaos Xylourgidis, Farida Ahangari, Patty J Lee, Vassilis Aidinis, Erica L Herzog, Robert Homer, Anton M Bennett, Naftali Kaminski
RATIONALE: Idiopathic Pulmonary Fibrosis (IPF) is a chronic fatal lung disease with dismal prognosis and no cure. The potential role of the ubiquitously expressed SH2 domain-containing-tyrosine phosphatase (SHP2) as a therapeutic target has not been studied in IPF Objectives: To determine the expression, mechanistic role and potential therapeutic utility of SHP2 in Pulmonary Fibrosis Methods: The effects of SHP2 overexpression and inhibition on fibroblast response to pro-fibrotic stimuli were analyzed in-vitro in primary human and mouse lung fibroblasts...
October 13, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27694325/rapamycin-attenuates-cardiac-fibrosis-in-experimental-uremic-cardiomyopathy-by-reducing-marinobufagenin-levels-and-inhibiting-downstream-pro-fibrotic-signaling
#10
Steven T Haller, Yanling Yan, Christopher A Drummond, Joe Xie, Jiang Tian, David J Kennedy, Victoria Y Shilova, Zijian Xie, Jiang Liu, Christopher J Cooper, Deepak Malhotra, Joseph I Shapiro, Olga V Fedorova, Alexei Y Bagrov
BACKGROUND: Experimental uremic cardiomyopathy causes cardiac fibrosis and is causally related to the increased circulating levels of the cardiotonic steroid, marinobufagenin (MBG), which signals through Na/K-ATPase. Rapamycin is an inhibitor of the serine/threonine kinase mammalian target of rapamycin (mTOR) implicated in the progression of many different forms of renal disease. Given that Na/K-ATPase signaling is known to stimulate the mTOR system, we speculated that the ameliorative effects of rapamycin might influence this pathway...
September 30, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27647831/imbalance-of-the-vanin-1-pathway-in-systemic-sclerosis
#11
Niloufar Kavian, Souad Mehlal, Wioleta Marut, Amélie Servettaz, Caroline Giessner, Christophe Bourges, Carole Nicco, Christiane Chéreau, Hervé Lemaréchal, Marie-Flore Dutilh, Olivier Cerles, Philippe Guilpain, Vincent Vuiblet, Sandrine Chouzenoux, Franck Galland, Isabelle Quere, Bernard Weill, Philippe Naquet, Frédéric Batteux
Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and visceral organs and vascular alterations. SSc pathophysiology involves systemic inflammation and oxidative stress. Because the vanin-1 gene (vnn1) encodes an enzyme with pantetheinase activity that converts vasculoprotective pantethine into profibrotic pantothenic acid and pro-oxidant cystamine, we tested this pathway in the pathophysiology of SSc. Activation of the vanin-1/pantetheinase pathway was investigated in wild-type BALB/c mice with hypochlorous acid (HOCl)-induced SSc by ELISA and Western blotting...
September 19, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27642633/adam17-substrate-release-in-proximal-tubule-drives-kidney-fibrosis
#12
Eirini Kefaloyianni, Muthu Lakshmi Muthu, Jakob Kaeppler, Xiaoming Sun, Venkata Sabbisetti, Athena Chalaris, Stefan Rose-John, Eitan Wong, Irit Sagi, Sushrut S Waikar, Helmut Rennke, Benjamin D Humphreys, Joseph V Bonventre, Andreas Herrlich
Kidney fibrosis following kidney injury is an unresolved health problem and causes significant morbidity and mortality worldwide. In a study into its molecular mechanism, we identified essential causative features. Acute or chronic kidney injury causes sustained elevation of a disintegrin and metalloprotease 17 (ADAM17); of its cleavage-activated proligand substrates, in particular of pro-TNFα and the EGFR ligand amphiregulin (pro-AREG); and of the substrates' receptors. As a consequence, EGFR is persistently activated and triggers the synthesis and release of proinflammatory and profibrotic factors, resulting in macrophage/neutrophil ingress and fibrosis...
August 18, 2016: JCI Insight
https://www.readbyqxmd.com/read/27638633/agmatine-protects-rat-liver-from-nicotine-induced-hepatic-damage-via-antioxidative-antiapoptotic-and-antifibrotic-pathways
#13
Nagla A El-Sherbeeny, Manar A Nader, Ghalia M Attia, Hayam Ateyya
Tobacco smoking with its various forms is a global problem with proved hazardous effects to human health. The present work was planned to study the defending role of agmatine (AGM) on hepatic oxidative stress and damage induced by nicotine in rats. Thirty-two rats divided into four groups were employed: control group, nicotine-only group, AGM group, and AGM-nicotine group. Measurements of serum hepatic biochemical markers, lipid profile, and vascular cell adhesion molecule-1 were done. In addition, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) activity, and nitrate/nitrite (NOx) levels were estimated in the liver homogenates...
September 16, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/27611832/the-role-of-the-rho-rock-pathway-in-ang-ii-and-tgf-%C3%AE-1-induced-atrial-remodeling
#14
Li-Juan Liu, Feng-Juan Yao, Gui-Hua Lu, Cheng-Gui Xu, Zhe Xu, Kai Tang, Yun-Jiu Cheng, Xiu-Ren Gao, Su-Hua Wu
OBJECTIVES: To study the role of the Rho/ROCK pathway in Ang II and TGF-β1-induced atrial remodeling. METHODS AND RESULTS: A canine atrial fibrillation (AF) model was established by rapid atrial pacing (RAP) of the left atrium. The roles of TGF-β1, the RhoA/ROCK signaling pathway and connective tissue growth factor (CTGF) in atrial remodeling were studied via both in vitro and in vivo experiments. Each of the dogs that received RAP developed persistent AF within 4 weeks...
2016: PloS One
https://www.readbyqxmd.com/read/27595139/classical-dendritic-cells-mediate-fibrosis-directly-via-the-retinoic-acid-pathway-in-severe-eye-allergy
#15
Sarah D Ahadome, Rose Mathew, Nancy J Reyes, Priyatham S Mettu, Scott W Cousins, Virginia L Calder, Daniel R Saban
Fibrosis is a shared end-stage pathway to lung, liver, and heart failure. In the ocular mucosa (conjunctiva), fibrosis leads to blindness in trachoma, pemphigoid, and allergy. The indirect fibrogenic role of DCs via T cell activation and inflammatory cell recruitment is well documented. However, here we demonstrate that DCs can directly induce fibrosis. In the mouse model of allergic eye disease (AED), classical CD11b(+) DCs in the ocular mucosa showed increased activity of aldehyde dehydrogenase (ALDH), the enzyme required for retinoic acid synthesis...
August 4, 2016: JCI Insight
https://www.readbyqxmd.com/read/27587602/diuretics-prevent-rho-kinase-activation-and-expression-of-profibrotic-oxidative-genes-in-the-hypertensive-aortic-wall
#16
Patricio Araos, David Mondaca, Jorge E Jalil, Cristián Yañez, Ulises Novoa, Italo Mora, María Paz Ocaranza
BACKGROUND: Diuretics are current antihypertensive drugs since they reduce blood pressure and cardiovascular risk. Increased vascular tone is modulated in a relevant way by the RhoA/Rho-kinase (ROCK) pathway, by acting on vascular smooth muscle cell contraction. This pathway has also proremodeling vascular effects. There are few data on the role of diuretics on both vascular ROCK activation and on proremodeling effects. We assessed the effects of hydrochlorothiazide (HCTZ) and spironolactone (spiro) alone and in combination with the ROCK inhibitor fasudil (FAS) on ROCK activation, gene expression of proremodeling markers and on hypertrophy in the aortic wall of hypertensive rats...
September 1, 2016: Therapeutic Advances in Cardiovascular Disease
https://www.readbyqxmd.com/read/27584972/preoperative-plasma-aldosterone-and-the-risk-of-atrial-fibrillation-after-coronary-artery-bypass-surgery-a-prospective-cohort-study
#17
Joachim Alexandre, Eric Saloux, Mathieu Chequel, Stéphane Allouche, Pierre Ollitrault, Anne-Flore Plane, Damien Legallois, Marc-Olivier Fischer, Vladimir Saplacan, Dimitrios Buklas, Fabien Labombarda, Katrien Blanchart, Joe-Elie Salem, Marie Nowoczyn, Paolo-Emilio Puddu, Alain Manrique, Jean-Jacques Parienti, Paul Milliez
OBJECTIVE: Postoperative atrial fibrillation (POAF) is associated with poor outcomes after coronary artery bypass graft (CABG) surgery. We aimed to assess the additional value of preoperative plasma aldosterone levels, a biomarker promoting proarrhythmic and profibrotic pathways, for predicting POAF after CABG. METHODS: We conducted a prospective cohort study involving consecutive patients with left ventricular ejection fraction (LVEF) more than 50% requiring elective CABG in our university hospital...
August 31, 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27553363/the-molecular-pathogenesis-of-morphoea-from-genetics-to-future-treatment-targets
#18
A M Saracino, C P Denton, C H Orteu
A number of immunoinflammatory and profibrotic mechanisms are recognised in the pathogenesis of broad sclerotic skin processes, and more specifically, morphoea. However, precise aetiopathogenesis is complex and remains unclear. Morphoea is clinically heterogeneous, with variable anatomical patterning, depth of tissue involvement, and sclerotic, inflammatory, atrophic and dyspigmented morphology. Underlying mechanisms determining these reproducible clinical subsets are poorly understood, but of great clinical and therapeutic relevance...
August 24, 2016: British Journal of Dermatology
https://www.readbyqxmd.com/read/27531241/exposure-to-human-immunodeficiency-virus-hepatitis-c-virus-in-hepatic-and-stellate-cell-lines-reveals-cooperative-profibrotic-transcriptional-activation-between-viruses-and-cell-types
#19
Shadi Salloum, Jacinta A Holmes, Rohit Jindal, Shyam S Bale, Cynthia Brisac, Nadia Alatrakchi, Anna Lidofsky, Annie J Kruger, Dahlene N Fusco, Jay Luther, Esperance A Schaefer, Wenyu Lin, Martin L Yarmush, Raymond T Chung
: Human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection accelerates progressive liver fibrosis; however, the mechanisms remain poorly understood. HCV and HIV independently induce profibrogenic markers transforming growth factor beta-1 (TGFβ1) (mediated by reactive oxygen species [ROS]) and nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) in hepatocytes and hepatic stellate cells in monoculture; however, they do not account for cellular crosstalk that naturally occurs...
December 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27525312/hybrid-inhibitor-of-peripheral-cannabinoid-1-receptors-and-inducible-nitric-oxide-synthase-mitigates-liver-fibrosis
#20
Resat Cinar, Malliga R Iyer, Ziyi Liu, Zongxian Cao, Tony Jourdan, Katalin Erdelyi, Grzegorz Godlewski, Gergő Szanda, Jie Liu, Joshua K Park, Bani Mukhopadhyay, Avi Z Rosenberg, Jeih-San Liow, Robin G Lorenz, Pal Pacher, Robert B Innis, George Kunos
Liver fibrosis, a consequence of chronic liver injury and a way station to cirrhosis and hepatocellular carcinoma, lacks effective treatment. Endocannabinoids acting via cannabinoid-1 receptors (CB1R) induce profibrotic gene expression and promote pathologies that predispose to liver fibrosis. CB1R antagonists produce opposite effects, but their therapeutic development was halted due to neuropsychiatric side effects. Inducible nitric oxide synthase (iNOS) also promotes liver fibrosis and its underlying pathologies, but iNOS inhibitors tested to date showed limited therapeutic efficacy in inflammatory diseases...
July 21, 2016: JCI Insight
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