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TGF beta AND Pirfenidone

Chaoming Zhou, Fang Liu, Phillip H Gallo, Mark E Baratz, Sandeep Kathju, Latha Satish
BACKGROUND: Dupuytren's disease (DD) is a complex fibro-proliferative disorder of the hand that is often progressive and eventually can cause contractures of the affected fingers. Transforming growth factor beta (TGF-β1) has been implicated as a key stimulator of myofibroblast activity and fascial contraction in DD. Pirfenidone (PFD) is an active small molecule shown to inhibit TGF-β1-mediated action in other fibrotic disorders. This study investigates the efficacy of PFD in vitro in inhibiting TGF-β1-mediated cellular functions leading to Dupuytren's fibrosis...
November 11, 2016: BMC Musculoskeletal Disorders
Zulfu Bayhan, Sezgin Zeren, Fatma Emel Kocak, Cengiz Kocak, Raziye Akcılar, Ertugrul Kargı, Cagrı Tiryaki, Faik Yaylak, Aydın Akcılar
BACKGROUND: Pirfenidone (PF) is a potent antifibrotic and anti-inflammatory agent. We investigated the protective effect of PF against postoperative intra-abdominal adhesions. MATERIAL AND METHODS: Thirty male Sprague-Dawley rats were divided into three groups (n = 10 in each group). In group 1 (control), adhesion induction was performed by cecal abrasion, and no treatment was administered. In group 2 (vehicle), for 2 wk after adhesion induction, 0.4%-carboxymethylcellulose was administered by gavage...
April 2016: Journal of Surgical Research
Lynda Aoudjehane, Pierre-Yves Boelle, Grégoire Bisch, Rolland Delelo, François Paye, Olivier Scatton, Chantal Housset, Jérôme Becquart, Yvon Calmus, Filomena Conti
We have developed a culture model to assess antifibrotic drugs using normal human liver myofibroblasts (HLMFs) obtained from 31 subjects. Activation was evaluated in terms of α-smooth muscle actin (α-SMA) and collagen 1 (Coll1) expression using RT-PCR, and proliferation as the uptake of 5-ethynil-2'-deoxyuridine. Under analysis of variance, between-subject differences accounted for 70% of all variability and inter-experiment differences for 30%. The sensitivity of the model was determined by quantifying the effects in terms of relative expression, which were 0...
June 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
Virgil A S H Dalm, Willem A Dik, Hok B Thio, Bernt van den Blink, P Martin van Hagen, Paul L A van Daele
Fibrosis is one of the leading causes of morbidity and mortality in the Western world. This disorder is characterised by an abnormal and increased rate of fibroblast proliferation and by an excessive deposition of connective tissue. The key player in fibrosis is the myofibroblast. Fibrosis leads to loss of organ structure and, eventually, to decrease in organ function. To date, there are hardly any effective therapies for the treatment of patients with fibrosis. Pirfenidone targets the myofibroblast and is effective in the treatment of idiopathic pulmonary fibrosis...
2015: Nederlands Tijdschrift Voor Geneeskunde
Seo-Hyun Choi, Jae-Kyung Nam, Junho Jang, Hae-June Lee, Yoon-Jin Lee
Radiotherapy is a widely used treatment for many tumors. Combination therapy using anti-angiogenic agents and radiation has shown promise; however, these combined therapies are reported to have many limitations in clinical trials. Here, we show that radiation transformed tumor endothelial cells (ECs) to fibroblasts, resulting in reduced vascular endothelial growth factor (VEGF) response and increased Snail1, Twist1, Type I collagen, and transforming growth factor (TGF)-β release. Irradiation of radioresistant Lewis lung carcinoma (LLC) tumors greater than 250 mm³ increased collagen levels, particularly in large tumor vessels...
June 26, 2015: Biochemical and Biophysical Research Communications
Inge M Westra, Dorenda Oosterhuis, Geny M M Groothuis, Peter Olinga
Two important signaling pathways in liver fibrosis are the PDGF- and TGFβ pathway and compounds inhibiting these pathways are currently developed as antifibrotic drugs. Testing antifibrotic drugs requires large numbers of animal experiments with high discomfort. Therefore, a method to study these drugs ex vivo was developed using precision-cut liver slices from fibrotic rat livers (fPCLS), representing an ex vivo model with a multicellular fibrotic environment. We characterized the fibrotic process in fPCLS from rat livers after 3 weeks of bile duct ligation (BDL) during incubation and tested compounds predominantly inhibiting the TGFβ pathway (perindopril, valproic acid, rosmarinic acid, tetrandrine and pirfenidone) and PDGF pathway (imatinib, sorafenib and sunitinib)...
2014: PloS One
Enrico Conte, Elisa Gili, Evelina Fagone, Mary Fruciano, Maria Iemmolo, Carlo Vancheri
Pirfenidone is an orally active small molecule that has been shown to inhibit the progression of fibrosis in animal models and in patients with idiopathic pulmonary fibrosis. Although pirfenidone exhibits well documented antifibrotic and antiinflammatory activities, in vitro and in vivo, its molecular targets and mechanisms of action have not been elucidated. In this study, we investigated the effects of pirfenidone on proliferation, TGF-β-induced differentiation and fibrogenic activity of primary human lung fibroblasts (HLFs)...
July 16, 2014: European Journal of Pharmaceutical Sciences
Jing Wang, Yangfan Yang, Jiangang Xu, Xianchai Lin, Kaili Wu, Minbin Yu
PURPOSE: To investigate the effects of pirfenidone (PFD) on the migration, differentiation, and proliferation of retinal pigment epithelial (RPE) cells and demonstrate whether the drug induces cytotoxicity. METHODS: Human RPE cells (line D407) were treated with various concentrations of PFD. Cell migration was measured with scratch assay. The protein levels of fibronectin (FN), connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), transforming growth factor beta (TGFβS), and Smads were assessed with western blot analyses...
2013: Molecular Vision
Xu Ji, Yukiko Naito, Huachun Weng, Xiao Ma, Kosuke Endo, Naoko Kito, Nariaki Yanagawa, Yang Yu, Jie Li, Naoharu Iwai
Pirfenidone (PFD) is a novel anti-fibrotic agent that targets TGFβ. However, the mechanisms underlying its renoprotective properties in hypertension-induced renal injury are poorly understood. We investigated the renoprotective properties of PFD and clarified its renoprotective mechanisms in a rat hypertension-induced renal injury model. Dahl salt-sensitive rats were fed a high-salt diet with or without 1% PFD for 6 weeks. During the administration period, we examined the effects of PFD on blood pressure and renal function...
2013: Biomedical Research
Zheng Xiao, Cheng-wen Li, Juan Shan, Lei Luo, Li Feng, Jun Lu, Sheng-fu Li, Dan Long, You-ping Li
OBJECTIVE: To reveal interventions for chronic cyclosporine A nephrotoxicity (CCN) and provide new targets for further studies, we analyzed all relevant studies about interventions in renal cell apoptosis. DATA SOURCES: We collected all relevant studies about interventions for cyclosporine A (CsA)-induced renal cell apoptosis in Medline (1966 to July 2010), Embase (1980 to July 2010) and ISI (1986 to July 2010), evaluated their quality, extracted data following PICOS principles and synthesized the data...
2013: Chinese Medical Journal
Kyoung In Jung, Jun-Sub Choi, Hyun Kyung Kim, Sun Young Shin
PURPOSE: To evaluate the usefulness of an anti-transforming growth factor-β (TGF-β) agent, pirfenidone (PFD) on postoperative inflammation and fibrosis following strabismus surgery in rabbits. METHODS: Both eyes of 16 New Zealand white rabbits underwent reinsertion of the superior rectus muscle (SRM). After reinsertion of the SRM, PFD-loaded liposomes (0.5 mg/ml) were injected into the right eye (PFD group) and normal saline-loaded liposomes was injected into the left eye (control group), subconjunctivally (0...
September 2012: Current Eye Research
Jean-Jacques Boffa, Jean-Claude Dussaule, Pierre Ronco, Christos Chatziantoniou
Despite the use of angiotensin blockers, chronic kidney diseases still progress. New therapeutic approaches aim to strengthen and to complete angiotensin blocker effects. Endothelin receptor antagonists, in addition to angiotensin blockers reduce blood pressure and urinary albumin excretion in diabetic nephropathies but can induce fluid overload. A second therapeutic approach consists in preventing the development of interstitial renal fibrosis which is a prognostic factor of CKD. Transforming growth factor-beta (TGF-beta) plays a major role in this process...
January 2012: La Revue du Praticien
Qiongjing Yuan, Linghao Wang, Fangfang Zhang, Rui Wang, Xiao Fu, Zhangzhe Peng, Wangbin Ning, Gaoyun Hu, Zhaohe Wang, Lijian Tao
OBJECTIVES: The present study was designed to investigate the potential effects and mechanism of fluorofenidone (AKF-PD) on transforming growth factor beta1 (TGF-beta1)-induced tubular epithelial-mesenchymal transition (EMT) and the expression of connective tissue growth factor (CTGF) in human proximal tubular epithelial cells. METHODS: HK-2 cells were pretreated with AKF-PD, pirfenidone (PFD), Losartan, and SB431542 (an inhibitor of TGF-beta type I receptor). The pretreated HK-2 cells were subsequently co-treated with TGF-beta1 (5 ng/ml)...
December 2011: Die Pharmazie
Nicholas Hoque, Marianne Thoresen, Kristian Aquilina, Sarah Hogan, Andrew Whitelaw
BACKGROUND: Post-haemorrhagic ventricular dilatation (PHVD) after intraventricular haemorrhage (IVH) remains a significant problem in preterm infants. Due to serious disadvantages of ventriculoperitoneal shunt dependence, there is an urgent need for non-surgical interventions. Considerable experimental and clinical evidence implicates transforming growth factor β (TGFβ) in the pathogenesis of PHVD. Colchicine and decorin are both compounds with anti-TGFβ properties. The former downregulates TGFβ production and is in clinical use for another fibrotic disease, and the latter inactivates TGFβ...
2011: Neonatology
Jun-wei Li, Xiu-wei Shen, Wei Sun, Min Xiao, Shu-hua Tong, Xi-chong Yu, Zhong-qiu Lu, Guo-xin Hu
OBJECTIVE: To study the curative effects of pirfenidone (PF) on pulmonary fibrosis induced by paraquat (PQ) in mice and to provide the theoretical basis for clinical treatment. METHODS: Ninety adult healthy male ICR mice were randomly divided into six groups: control group, PQ group, 2 mg/kg Dexamethasone group, 25 mg/kg PF group, 50 mg/kg PF group and 100 mg/kg PF group, there were 15 mice in each group. The corresponding volume of normal saline was given to the each mouse in control group according to the weight, after 2 h 0...
February 2011: Chinese Journal of Industrial Hygiene and Occupational Diseases
Hyunmi Kim, Youn-Hee Choi, Soo Jung Park, Sang Yeul Lee, Sung Joo Kim, Ilo Jou, Koung Hoon Kook
PURPOSE: The aim of this study was to determine the antifibrotic effects of pirfenidone in orbital fibroblasts of patients with thyroid-associated ophthalmopathy (TAO). METHODS: The effects of interleukin (IL)-1beta and of fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), and transforming growth factor (TGF)-beta on the induction of tissue inhibitors of metalloproteinases (TIMP)-1 were assessed in orbital fibroblasts of TAO patients. TIMP-1 protein levels were measured by ELISA and Western blot analyses, and TIMP-1 activity was assessed by reverse zymography...
June 2010: Investigative Ophthalmology & Visual Science
Koji Takakuta, Akira Fujimori, Toshihiro Chikanishi, Akira Tanokura, Yoshiyuki Iwatsuki, Masanori Yamamoto, Hidenori Nakajima, Masamichi Okada, Hiroyuki Itoh
Renal fibrosis is the final common pathway of chronic kidney disease, and its progression predicts the degree of renal dysfunction. We investigated the renoprotective properties of pirfenidone in a remnant kidney model of chronic renal failure to determine its pharmacological potency compared to enalapril. Five-sixths nephrectomized rats were fed diet containing pirfenidone (approximately 700mg/kg/day) for 8weeks. Pirfenidone steadily inhibited the progression of proteinuria, but not to a significant degree...
March 10, 2010: European Journal of Pharmacology
Satish P RamachandraRao, Yanqing Zhu, Timothy Ravasi, Tracy A McGowan, Irene Toh, Stephen R Dunn, Shinichi Okada, Michael A Shaw, Kumar Sharma
Although several interventions slow the progression of diabetic nephropathy, current therapies do not halt progression completely. Recent preclinical studies suggested that pirfenidone (PFD) prevents fibrosis in various diseases, but the mechanisms underlying its antifibrotic action are incompletely understood. Here, we evaluated the role of PFD in regulation of the extracellular matrix. In mouse mesangial cells, PFD decreased TGF-beta promoter activity, reduced TGF-beta protein secretion, and inhibited TGF-beta-induced Smad2-phosphorylation, 3TP-lux promoter activity, and generation of reactive oxygen species...
August 2009: Journal of the American Society of Nephrology: JASN
Xianchai Lin, Minbin Yu, Kaili Wu, Hongzhi Yuan, Hua Zhong
PURPOSE: To investigate the effect of pirfenidone, a novel antifibrotic agent, on proliferation, migration, and collagen contraction of human Tenon's fibroblasts (HTFs). METHODS: After treatment of HTFs with pirfenidone, cell proliferation was measured by MTT assay. Cell migration was investigated by scratch assay. Contractility was evaluated in fibroblast-populated collagen gels. Cell viability was determined by trypan blue exclusion assay. The expression of TGF-beta1, -beta2, and -beta3 was estimated with RT-PCR, Western blot, and immunofluorescence analyses...
August 2009: Investigative Ophthalmology & Visual Science
Vasiliki Kalliopi K Bournia, Panayiotis G Vlachoyiannopoulos, Carlo Selmi, Haralampos M Moutsopoulos, M Eric Gershwin
Systemic sclerosis (SSc) is a chronic autoimmune disease with clinical manifestations resulting from immune activation, fibrosis development, and damage of small blood vessels. Our aim was to critically illustrate the available data on the new treatments proposed for SSc to provide a clinically oriented overview of the current evidence. PubMed was used for literature search using "scleroderma" and "therapy" to identify all articles published on indexed journals between 1972 and 2008. The search was limited to publications in English and produced a total of 3,441 references, which included 735 review articles...
June 2009: Clinical Reviews in Allergy & Immunology
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