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https://www.readbyqxmd.com/read/28921394/combination-therapy-with-pirfenidone-plus-prednisolone-ameliorates-paraquat-induced-pulmonary-fibrosis
#1
Rokhsana Rasooli, Fatemeh Pourgholamhosein, Younes Kamali, Fatemeh Nabipour, Ali Mandegary
Pirfenidone is known to slow the decline in vital capacity and increase survival in idiopathic pulmonary fibrosis (IPF). Besides, administration of glucocorticoids, e.g., prednisolone has been the conventional strategy to the treatment of patients with this disease, although their efficacy is under debate. Since multiple coactivated pathways are involved in the pathogenesis of IPF, combination therapy is a foundation strategy to cover many more synergetic mechanisms and increase response. The aim of the present study was to compare the therapeutic efficacy of prednisolone plus pirfenidone with pirfenidone alone in PQ-induced lung fibrosis...
September 18, 2017: Inflammation
https://www.readbyqxmd.com/read/28903945/complement-c5a-receptors-c5l2-and-c5ar-in-renal-fibrosis
#2
Ina V Martin, Annika Bohner, Peter Boor, Erdenechimeg Shagdarsuren, Ute Raffetseder, Frank Lammert, Jürgen Floege, Tammo Ostendorf, Susanne N Weber
Complement factor C5a has two known receptors, C5aR mediating pro-inflammatory effects and C5L2, a potential C5a scavenger. We previously identified C5a/C5aR signaling as a potent profibrotic pathway in the kidney. Here we tested for the first time the role of C5L2 in renal fibrosis. In unilateral ureteral obstruction (UUO)-induced kidney fibrosis, the expression of C5aR and C5L2 increased similarly and gradually as fibrosis progressed and was particularly prominent in injured dilated tubules. Genetic deficiency of either C5aR or C5L2 significantly reduced UUO-induced tubular injury...
September 13, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28890699/sphingosine-1-phosphate-signaling-as-a-target-in-hepatic-fibrosis-therapy
#3
REVIEW
Bárbara González-Fernández, Diana I Sánchez, Javier González-Gallego, María J Tuñón
Liver fibrosis is an excess production of extracellular matrix proteins as a result of chronic liver disease which leads to cell death and organ dysfunction. The key cells involved in fibrogenesis are resident hepatic stellate cells (HSCs) which are termed myofibroblasts after activation, acquiring contractile, proliferative, migratory and secretory capability. Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid with well-established effects on angiogenesis, carcinogenesis and immunity. Accumulating evidence demonstrates that this metabolite is involved in the profibrotic inflammatory process through the regulation of pleiotropic cell responses, such as vascular permeability, leukocyte infiltration, cell survival, migration, proliferation and HSCs differentiation to myofibroblasts...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28886261/syndecan-2-attenuates-radiation-induced-pulmonary-fibrosis-and-inhibits-fibroblast-activation-by-regulating-pi3k-akt-rock-pathway-via-cd148
#4
Konstantin Tsoyi, Sarah G Chu, Nasly G Patino-Jaramillo, Julie Wilder, Julian Villalba, Melanie Doyle-Eisele, Jacob McDonald, Xiaoli Liu, Souheil El-Chemaly, Mark A Perrella, Ivan O Rosas
RATIONALE: Radiation-induced pulmonary fibrosis is a severe complication of patients treated with thoracic irradiation. We have previously shown that syndecan-2 reduces fibrosis by exerting alveolar epithelial cytoprotective effects. Here, we investigate whether syndecan-2 attenuates radiation-induced pulmonary fibrosis by inhibiting fibroblast activation. METHODS: C57BL/6 wild type (WT) mice and transgenic (TG) mice that overexpress human syndecan-2 in alveolar macrophages were exposed to 14 Gy whole thoracic radiation...
September 8, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28873458/anti-fibrotic-effects-of-valproic-acid-in-experimental-peritoneal-fibrosis
#5
Elerson C Costalonga, Luiza J de Freitas, Deise da S P Aragone, Filipe M O Silva, Irene L Noronha
BACKGROUND: Progressive fibrous thickening of the peritoneal membrane is a complication of long-term peritoneal dialysis (PD). TGF-β/Smad pathway activation, inflammation, and neoangiogenesis play important roles in peritoneal membrane (PM) changes induced by PD. Recently, histone deacetilase inhibitors (HDACi) have shown anti-fibrotic and anti-inflammatory effects in different experimental models. These drugs prevent deacetylation of histones causing a loosen chromatin, which in turn induce the expression of some anti-fibrotic genes...
2017: PloS One
https://www.readbyqxmd.com/read/28864379/overexpression-of-heparin-binding-epidermal-growth-factor-like-growth-factor-mediates-liver-fibrosis-in-transgenic-mice
#6
Yongze Guo, Qian Ding, Lei Chen, Chenguang Ji, Huiyao Hao, Jia Wang, Wei Qi, Xiaoli Xie, Junji Ma, Aidi Li, Xiaoyu Jiang, Xiaotian Li, Huiqing Jiang
BACKGROUND: The role of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in liver fibrosis is not clear and is sometimes even contradictory. To clarify this role, a HB-EGF transgenic (Tg) mouse model was, for the first time, used to evaluate the functions of HB-EGF in liver fibrosis. MATERIALS AND METHODS: For the in vivo study, carbon tetrachloride injection and bile duct ligation treatment were used to induce liver fibrosis in HB-EGF Tg mice and wild-type (WT) mice, respectively...
August 2017: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/28860147/blockade-of-extracellular-heat-shock-protein-90-alpha-by-1g6-d7-attenuates-pulmonary-fibrosis-through-inhibiting-erk-signaling
#7
Hangming Dong, Lishan Luo, Mengchen Zou, Chaowen Huang, Xuan Wan, Yahui Hu, Yanqing Le, Haijin Zhao, Wei Li, Fei Zou, Shaoxi Cai
Pulmonary fibrosis is characterized by lung fibroblast activation and ECM deposition and has a poor prognosis.Heat shock protein 90 (Hsp90) participates in organ fibrosis and extracellular Hsp90α (eHsp90α) promotes fibroblast activation and migration. This study aimed to investigate whether a selective anti-Hsp90α monoclonal antibody, 1G6-D7, could attenuate lung fibrosis and whether 1G6-D7 presents protective effect by inactivating profibrotic pathway.Our results showed that eHsp90α was increased in mice with BLM-induced pulmonary fibrosis and that 1G6-D7 attenuated inflammation and collagen deposition in the lung...
August 31, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28860142/novel-therapeutic-roles-for-surfactant-inositols-and-phosphatidylglycerols-in-a-neonatal-piglet-ards-model-a-translational-study
#8
Dietmar Spengler, Supandi Winoto-Morbach, Sarah Kupsch, Christina Vock, Katharina Blöchle, Susanna Frank, Nele Rintz, Marie Diekötter, Harshavardhan Janga, Markus Weckmann, Sabine Fuchs, Andra B Schromm, Heinz Fehrenbach, Stefan Schütze, Martin F Krause
The biological and immune-protective properties of surfactant-derived phospholipids and phospholipid-subfractions in the context of neonatal inflammatory lung disease are widely unknown. Using a porcine neonatal triple-hit ARDS model (repeated airway lavage, overventilation, LPS instillation into airways), we assessed whether the supplementation of surfactant (poractant alfa, S) with inositol-derivatives (inositol-1,2,6-trisphosphate, IP3; phosphatidylinositol-3,5-bisphosphate, PIP2) or phosphatidylglycerol-subfractions (16:0/18:1-POPG; 18:1/18:1-DOPG) would result in improved clinical parameters, and sought to characterize changes in key inflammatory pathways behind these improvements...
August 31, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28846982/mir-200a-modulates-tgf-%C3%AE-1-induced-endothelial-to-mesenchymal-shift-via-suppression-of-grb2-in-haecs
#9
Hao Zhang, Jianguo Hu, Liming Liu
Endothelial-mesenchymal transition (EndMT) is closely associated with embryogenesis, injury restitution, tissue neogenesis, tumor progressions and viscera fibrosis. EndMT may occur in the proximal tubular endothelial cells, inducing fibroblasts to produce matrix and then accelerating the process of cardiac fibrosis. Transforming growth factor-β1 (TGF-β1), a profibrotic cytokine, was recently shown to be a crucial trigger of EndMT in tubular endothelial cells. Increasing evidence suggests that growth factor receptor-bound 2 (GRB2) dysfunction affects fibrocytes; thus, GRB2 may be a novel target for treating fibrosis...
August 25, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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
#10
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
#11
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
#12
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...
October 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28751525/pgc-1%C3%AE-protects-from-notch-induced-kidney-fibrosis-development
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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