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https://www.readbyqxmd.com/read/28804632/the-pattern-of-il-24-mda-7-and-its-cognate-receptors-expression-following-activation-of-human-hepatic-stellate-cells
#1
Iman Jamhiri, Seyed Younes Hosseini, Davood Mehrabani, Zahra Khodabandeh, Ramin Yaghobi, Razieh Dowran, Saber Zahri
Activation of hepatic stellate cells (HSCs) is the pivotal event during liver fibrosis. Interleukin (IL)-24/melanoma differentiation-associated gene-7 (mda-7) has attracted attention in the pathophysiology of some diseases, while its role in activation/suppression of human HSCs is still unclear. It is important to elucidate whether the expression levels of the IL-24/mda-7 protein and its receptors in HSC cells are changed following activation. LX-2 cells, a human hepatic stellate cell line were activated by a combination of leptin and serum starvation...
August 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28801314/macrophage-migration-inhibitory-factor-limits-renal-inflammation-and-fibrosis-by-counteracting-tubular-cell-cycle-arrest
#2
Sonja Djudjaj, Ina V Martin, Eva M Buhl, Nina J Nothofer, Lin Leng, Marta Piecychna, Jürgen Floege, Jürgen Bernhagen, Richard Bucala, Peter Boor
Renal fibrosis is a common underlying process of progressive kidney diseases. We investigated the role of macrophage migration inhibitory factor (MIF), a pleiotropic proinflammatory cytokine, in this process. In mice subjected to unilateral ureteral obstruction, genetic deletion or pharmacologic inhibition of MIF aggravated fibrosis and inflammation, whereas treatment with recombinant MIF was beneficial, even in established fibrosis. In two other models of progressive kidney disease, global Mif deletion or MIF inhibition also worsened fibrosis and inflammation and associated with worse kidney function...
August 11, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28791353/telmisartan-improves-vascular-remodeling-through-ameliorating-prooxidant-and-profibrotic-mechanisms-in-hypertension-via-the-involvement-of-transforming-growth-factor-%C3%AE-1
#3
Peijin Shang, Tianlong Liu, Wenxing Liu, Yuwen Li, Fang Dou, Yikai Zhang, Lijuan Sun, Tiejun Zhang, Zhihui Zhu, Fei Mu, Yi Ding, Aidong Wen
Vascular remodeling is a common complication and pathological basis of hypertension. Transforming growth factor‑β1 (TGF‑β1)/small mothers against decapentaplegic 3 (Smad3) is considered a potential therapeutic target for vascular remodeling in hypertension. The present study aimed to demonstrate the antifibrotic effects of telmisartan and examined the potential mechanisms associated with its prevention of vascular remodeling. Spontaneously hypertensive rats (SHRs) were treated with telmisartan (20 mg/kg), and vascular contractility, reactivity and oxidative stress were preliminarily evaluated...
August 4, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28751525/pgc-1%C3%AE-protects-from-notch-induced-kidney-fibrosis-development
#4
Seung Hyeok Han, Mei-Yan Wu, Bo Young Nam, Jung Tak Park, Tae-Hyun Yoo, Shin-Wook Kang, Jihwan Park, Frank Chinga, Szu-Yuan Li, Katalin Susztak
Kidney fibrosis is the histologic manifestation of CKD. Sustained activation of developmental pathways, such as Notch, in tubule epithelial cells has been shown to have a key role in fibrosis development. The molecular mechanism of Notch-induced fibrosis, however, remains poorly understood. Here, we show that, that expression of peroxisomal proliferation g-coactivator (PGC-1α) and fatty acid oxidation-related genes are lower in mice expressing active Notch1 in tubular epithelial cells (Pax8-rtTA/ICN1) compared to littermate controls...
July 27, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28711329/cardiac-reprogramming-factor-gata4-reduces-postinfarct-cardiac-fibrosis-through-direct-repression-of-the-profibrotic-mediator-snail
#5
Megumi Mathison, Vivek P Singh, Deepthi Sanagasetti, Lina Yang, Jaya Pratap Pinnamaneni, Jianchang Yang, Todd K Rosengart
OBJECTIVE: The administration of a variety of reprogramming factor cocktails has now been shown to reprogram cardiac fibroblasts into induced cardiomyocyte-like cells. However, reductions in ventricular fibrosis observed after reprogramming factor administration seem to far exceed the extent of induced cardiomyocyte-like cell generation in vivo. We investigated whether reprogramming factor administration might primarily play a role in activating antifibrotic molecular pathways. METHODS: Adult rat cardiac fibroblasts were infected with lentivirus encoding the transcription factors Gata4, Mef2c, or Tbx5, all 3 vectors, or a green fluorescent protein control vector...
June 21, 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28701516/blocking-tgf-%C3%AE-and-%C3%AE-catenin-epithelial-crosstalk-exacerbates-ckd
#6
Stellor Nlandu-Khodo, Surekha Neelisetty, Melanie Phillips, Marika Manolopoulou, Gautam Bhave, Lauren May, Peter E Clark, Haichun Yang, Agnes B Fogo, Raymond C Harris, M Mark Taketo, Ethan Lee, Leslie S Gewin
The TGF-β and Wnt/β-catenin pathways have important roles in modulating CKD, but how these growth factors affect the epithelial response to CKD is not well studied. TGF-β has strong profibrotic effects, but this pleiotropic factor has many different cellular effects depending on the target cell type. To investigate how TGF-β signaling in the proximal tubule, a key target and mediator of CKD, alters the response to CKD, we injured mice lacking the TGF-β type 2 receptor specifically in this epithelial segment...
July 12, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28655975/stromal-and-immune-cells-in-gut-fibrosis-the-myofibroblast-and-the-scarface
#7
REVIEW
Vassilis Valatas, Eirini Filidou, Ioannis Drygiannakis, George Kolios
Post-inflammatory scarring is the end-result of excessive extracellular matrix (ECM) accumulation and tissue architectural destruction. It represents a failure to effectively remodel ECM and achieve proper reinstitution and healing during chronic relapsing inflammatory processes. Scarring may affect the functionality of any organ, and in the case of inflammatory bowel disease (IBD)-associated fibrosis leads to stricture formation and often surgery to remove the affected bowel. The activated myofibroblast is the final effector cell that overproduces ECM under the influence of various mediators generated by an intense interplay of classic and non-classic immune cells...
2017: Annals of Gastroenterology: Quarterly Publication of the Hellenic Society of Gastroenterology
https://www.readbyqxmd.com/read/28651950/the-loss-of-kr%C3%A3-ppel-like-factor-15-in-foxd1-stromal-cells-exacerbates-kidney-fibrosis
#8
Xiangchen Gu, Sandeep K Mallipattu, Yiqing Guo, Monica P Revelo, Jesse Pace, Timothy Miller, Xiang Gao, Mukesh K Jain, Agnieszka B Bialkowska, Vincent W Yang, John C He, Changlin Mei
Large epidemiological studies clearly demonstrate that multiple episodes of acute kidney injury contribute to the development and progression of kidney fibrosis. Although our understanding of kidney fibrosis has improved in the past two decades, we have limited therapeutic strategies to halt its progression. Myofibroblast differentiation and proliferation remain critical to the progression of kidney fibrosis. Although canonical Wnt signaling can trigger the activation of myofibroblasts in the kidney, mediators of Wnt inhibition in the resident progenitor cells are unclear...
June 24, 2017: Kidney International
https://www.readbyqxmd.com/read/28641719/surfactant-protein-d-inhibits-interleukin-12p40-production-by-macrophages-through-the-sirp%C3%AE-rock-erk-signaling-pathway
#9
Rui Yamaguchi, Arisa Sakamoto, Takatoshi Yamamoto, Yasuji Ishimaru, Shinji Narahara, Hiroyuki Sugiuchi, Yasuo Yamaguchi
OBJECTIVE: Interleukin (IL)-12 has a pivotal profibrotic role in the development of idiopathic pulmonary fibrosis (IPF). Medical research trials based on IPF registry databases have actively recruited patients. Surfactant protein D (SP-D) is a useful biomarker in patients with IPF. SP-D binds to signal regulatory protein α (SIRPα), which acts as an inhibitory receptor, and this SP-D/SIRPα interaction may have an anti-inflammatory effect. Accordingly, the inhibitory effect of SP-D on IL-12p40 production by lipopolysaccharide (LPS)-stimulated macrophages was investigated...
June 2017: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/28635301/stem-cell-mediated-paracrine-signaling-alters-fibroplasia-in-human-vocal-fold-fibroblasts-in-vitro
#10
Nao Hiwatashi, Renjie Bing, Iv Kraja, Ryan C Branski
OBJECTIVES: Interactions between mesenchymal stem cells (MSCs) and native vocal fold fibroblasts (VFFs) have not been described in spite of promising preliminary data regarding the effects of MSCs on vocal fold repair in vivo. The current study employed a conditioned media (CM) model to investigate the paracrine effects of bone marrow-derived mesenchymal stem cells (BMSCs) on VFFs. METHODS: Human VFFs were treated with transforming growth factor-β1 (TGF-β1; 10 ng/mL), CM from human BMSCs following 48 hours of TGF-β1 stimulation, or CM+TGF-β1...
August 2017: Annals of Otology, Rhinology, and Laryngology
https://www.readbyqxmd.com/read/28629772/impact-of-the-cardiovascular-system-associated-adipose-tissue-on-atherosclerotic-pathology
#11
REVIEW
Dimitry A Chistiakov, Andrey V Grechko, Veronika A Myasoedova, Alexandra A Melnichenko, Alexander N Orekhov
Cardiac obesity makes an important contribution to the pathogenesis of cardiovascular disease. One of the important pathways of this contribution is the inflammatory process that takes place in the adipose tissue. In this review, we consider the role of the cardiovascular system-associated fat in atherosclerotic cardiovascular pathology and a non-atherosclerotic cause of coronary artery disease, such as atrial fibrillation. Cardiovascular system-associated fat not only serves as the energy store, but also releases adipokines that control local and systemic metabolism, heart/vascular function and vessel tone, and a number of vasodilating and anti-inflammatory substances...
June 8, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28626076/cardiac-fibroblast-transcriptome-analyses-support-a-role-for-interferogenic-profibrotic-and-inflammatory-genes-in-anti-ssa-ro-associated-congenital-heart-block
#12
Robert M Clancy, Androo J Markham, Tanisha Jackson, Sara E Rasmussen, Miroslav Blumenberg, Jill P Buyon
The signature lesion of SSA/Ro autoantibody-associated congenital heart block (CHB) is fibrosis and a macrophage infiltrate, supporting an experimental focus on cues influencing the fibroblast component. The transcriptomes of human fetal cardiac fibroblasts were analyzed using two complementary approaches. Cardiac injury conditions were simulated in vitro by incubating human fetal cardiac fibroblasts with supernatants from macrophages transfected with the SSA/Ro-associated hY3. The top ten upregulated transcripts in the stimulated fibroblasts reflected a type I interferon (IFN) response (e...
June 16, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28626027/selective-activation-of-epidermal-growth-factor-receptor-in-renal-proximal-tubule-induces-tubulointerstitial-fibrosis
#13
Jessica M Overstreet, Yinqiu Wang, Xin Wang, Aolei Niu, Leslie S Gewin, Bing Yao, Raymond C Harris, Ming-Zhi Zhang
Epidermal growth factor receptor (EGFR) has been implicated in the pathogenesis of diabetic nephropathy and renal fibrosis; however, the causative role of sustained EGFR activation is unclear. Here, we generated a novel kidney fibrotic mouse model of persistent EGFR activation by selectively expressing the EGFR ligand, human heparin-binding EGF-like growth factor (HB-EGF), in renal proximal tubule epithelium. Human HB-EGF expression increased tyrosine kinase phosphorylation of EGFR and the subsequent activation of downstream signaling pathways, including ERK and AKT, as well as the profibrotic TGF-β1/SMAD pathway...
June 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28598023/nintedanib-reduces-ventilation-augmented-bleomycin-induced-epithelial-mesenchymal-transition-and-lung-fibrosis-through-suppression-of-the-src-pathway
#14
Li-Fu Li, Kuo-Chin Kao, Yung-Yang Liu, Chang-Wei Lin, Ning-Hung Chen, Chung-Shu Lee, Chih-Wei Wang, Cheng-Ta Yang
Mechanical ventilation (MV) used in patients with acute respiratory distress syndrome (ARDS) can increase lung inflammation and pulmonary fibrogenesis. Src is crucial in mediating the transforming growth factor (TGF)-β1-induced epithelial-mesenchymal transition (EMT) during the fibroproliferative phase of ARDS. Nintedanib, a multitargeted tyrosine kinase inhibitor that directly blocks Src, has been approved for the treatment of idiopathic pulmonary fibrosis. The mechanisms regulating interactions among MV, EMT and Src remain unclear...
June 9, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28585302/rictor-mammalian-target-of-rapamycin-complex-2-promotes-macrophage-activation-and-kidney-fibrosis
#15
Jiafa Ren, Jianzhong Li, Ye Feng, Bingyan Shu, Yuan Gui, Wei Wei, Weichun He, Junwei Yang, Chunsun Dai
Mammalian target of rapamycin (mTOR) signalling controls many essential cellular functions. However, the role of Rictor/mTOR complex 2 (mTORC2) in regulating macrophage activation and kidney fibrosis remains largely unknown. We report here that Rictor/mTORC2 was activated in macrophages from the fibrotic kidneys of mice. Ablation of Rictor in macrophages reduced kidney fibrosis, inflammatory cell accumulation, macrophage proliferation and polarization after unilateral ureter obstruction or ischaemia/reperfusion injury...
June 6, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28562065/role-of-platelet-derived-tgf-%C3%AE-1-and-ros-in-radiation-induced-organ-fibrosis
#16
Jasimuddin Ahamed, Jeffrey Laurence
SIGNIFICANCE: This review evaluates the role of platelet-derived TGF-β1 in oxidative stress-linked pathologic fibrosis, with an emphasis on the heart and kidney, using ionizing radiation as a clinically relevant stimulus. Current radiation-induced organ fibrosis interventions focus on pan-neutralization of transforming growth factor (TGF)-β1 or use of anti-oxidants and anti-proliferative agents, with limited clinical efficacy. Recent Advances: Pathologic fibrosis represents excessive accumulation of collagen and other extracellular matrix (ECM) components following dysregulation of a balance between ECM synthesis and degradation...
May 31, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28546006/atrial-myofibroblast-activation-and-connective-tissue-formation-in-a-porcine-model-of-atrial-fibrillation-and-reduced-left-ventricular-function
#17
Patrick Lugenbiel, Fabian Wenz, Katharina Govorov, Pascal Syren, Hugo A Katus, Dierk Thomas
AIMS: Atrial fibrillation (AF) is associated with fibrosis that slows electrical conduction and causes perpetuation of the arrhythmia. The molecular characterization of AF pathophysiology may provide novel therapeutic options. This study was designed to elucidate profibrotic signaling and myofibroblast activation in a porcine model of atrial tachypacing-induced AF and reduced left ventricular function. MATERIALS AND METHODS: Ten domestic pigs were randomized to sinus rhythm (SR) or AF groups...
July 15, 2017: Life Sciences
https://www.readbyqxmd.com/read/28486700/dysregulation-of-the-adam17-notch-signalling-pathways-in-endometriosis-from-oxidative-stress-to-fibrosis
#18
Iñaki González-Foruria, Pietro Santulli, Sandrine Chouzenoux, Francisco Carmona, Charles Chapron, Frédéric Batteux
STUDY QUESTION: Is oxidative stress associated with the A disintegrin and metalloproteases (ADAM) metallopeptidase domain 17 (ADAM17)/Notch signalling pathway and fibrosis in the development of endometriosis? SUMMARY ANSWER: Oxidative stress is correlated with hyperactivation of the ADAM17/Notch signalling pathway and a consequent increase in fibrosis in patients with endometriosis. WHAT IS KNOWN ALREADY: It is nowadays accepted that oxidative stress plays an important role in the onset and progression of endometriosis...
May 9, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28469078/mir-21-is-associated-with-fibrosis-and-right-ventricular-failure
#19
Sushma Reddy, Dong-Qing Hu, Mingming Zhao, Eddie Blay, Nefthi Sandeep, Sang-Ging Ong, Gwanghyun Jung, Kristina B Kooiker, Michael Coronado, Giovanni Fajardo, Daniel Bernstein
Combined pulmonary insufficiency (PI) and stenosis (PS) is a common long-term sequela after repair of many forms of congenital heart disease, causing progressive right ventricular (RV) dilation and failure. Little is known of the mechanisms underlying this combination of preload and afterload stressors. We developed a murine model of PI and PS (PI+PS) to identify clinically relevant pathways and biomarkers of disease progression. Diastolic dysfunction was induced (restrictive RV filling, elevated RV end-diastolic pressures) at 1 month after generation of PI+PS and progressed to systolic dysfunction (decreased RV shortening) by 3 months...
May 4, 2017: JCI Insight
https://www.readbyqxmd.com/read/28469072/uncoupling-of-the-profibrotic-and-hemostatic-effects-of-thrombin-in-lung-fibrosis
#20
Barry S Shea, Clemens K Probst, Patricia L Brazee, Nicholas J Rotile, Francesco Blasi, Paul H Weinreb, Katharine E Black, David E Sosnovik, Elizabeth M Van Cott, Shelia M Violette, Peter Caravan, Andrew M Tager
Fibrotic lung disease, most notably idiopathic pulmonary fibrosis (IPF), is thought to result from aberrant wound-healing responses to repetitive lung injury. Increased vascular permeability is a cardinal response to tissue injury, but whether it is mechanistically linked to lung fibrosis is unknown. We previously described a model in which exaggeration of vascular leak after lung injury shifts the outcome of wound-healing responses from normal repair to pathological fibrosis. Here we report that the fibrosis produced in this model is highly dependent on thrombin activity and its downstream signaling pathways...
May 4, 2017: JCI Insight
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