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cyclosporine fibroblast

Jinyu Chi, Lei Wang, Xiaohui Zhang, Yu Fu, Yue Liu, Wenjia Chen, Wenxiu Liu, Zhiyu Shi, Xinhua Yin
Cyclosporin A (CsA) is an effective immunosuppressive agent, but its myocardial toxicity limits its widespread and long-term clinical application. In this study, CsA treatment led to damages in myocardial fiber structure, an increase in myocardial fibrosis, and changes in heart size and shape; moreover, the degree of damage was exacerbated with prolonged drug application and increases in dose. However, the mechanism is not clear; therefore, the purpose of this study was to reveal the mechanism of CsA-induced myocardial fibrosis and identify a new target for the prevention and treatment of CsA-induced myocardial injury...
March 1, 2018: Biochimie
Casey Ritchhart, Anita Joy
Gingival Overgrowth (GO) is an undesirable result of certain drugs like Cyclosporine A (CsA). Histopathology of GO shows hyperplasia of gingival epithelium, expansion of connective tissue with increased collagen, or a combination. Factors such as age, gender, oral hygiene, duration, and dosage also influence onset and severity of GO. One of the mechanisms behind uncontrolled cell proliferation in drug-induced GO is inhibition of apoptotic pathways, with a consequent effect on normal cell turnover. Our objective was to determine if UV photo-treatment would activate apoptosis in the gingival fibroblast component...
February 7, 2018: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
Mustapha Irnaten, Alexander Zhdanov, Deirdre Brennan, Thomas Crotty, Abbot Clark, Dmitri Papkovsky, Colm O'Brien
Purpose: Optic nerve cupping in glaucoma is characterized by remodeling of the extracellular matrix (ECM) and fibrosis in the lamina cribrosa (LC). We have previously shown that glaucoma LC cells express raised levels of ECM genes and have elevated intracellular calcium ([Ca2+]i). Raised [Ca2+]i is known to promote proliferation, activation, and contractility in fibroblasts via the calcineurin-NFAT (nuclear factor of activated T-cells) signaling pathway. In this study, we examine NFAT expression in normal and glaucoma LC cells, and investigate the effect of cyclosporin A (CsA, a known inhibitor of NFAT activity) on [Ca2+]i and ECM gene expression in normal and glaucoma LC cells...
February 1, 2018: Investigative Ophthalmology & Visual Science
Hojjat-Allah Abbaszadeh, Ali Asghar Peyvandi, Yousef Sadeghi, Akram Safaei, Mona Zamanian-Azodi, Maryam Sadat Khoramgah, Mostafa Rezaei-Tavirani
Introduction: Periodontitis is a set of inflammatory disorders characterized by periodontal attachment loss and alveolar bone resorption. Because of deficiency in periodontitis mechanical therapy, this study was aimed to explore the molecular influence of the erbiumdoped: yttrium aluminum garnet (Er:YAG) laser and cyclosporin A (CsA) on human gingival fibroblasts (HGFs) for improvement in periodontal diseases therapy. Methods: We focused on articles that studied the proteome profiles of HGFs after treatment with laser irradiation and application of CsA...
2017: Journal of Lasers in Medical Sciences
So-Yeon Kim, Ho-Chang Jeong, Soon-Ki Hong, Mi-Ok Lee, Seung-Ju Cho, Hyuk-Jin Cha
Small molecules to selectively induce cell death of undifferentiated human pluripotent stem cells (hPSCs) have been developed with the aim of lowering the risk of teratoma formation during hPSC-based cell therapy. In this context, we have reported that Quercetin (QC) induces cell death selectively in hESCs via p53 mitochondrial localization. However, the detailed molecular mechanism by which hESCs undergo selective cell death induced by QC remains unclear. Herein, we demonstrate that mitochondrial reactive oxygen species (ROS), strongly induced by QC in human embryonic stem cells (hESCs) but not in human dermal fibroblasts (hDFs), were responsible for QC-mediated hESC's cell death...
September 12, 2017: Oncotarget
Erdal Uysal, Mehmet Dokur
PURPOSE: This study aims to examine and compare the effects of immunosuppressant cyclosporine A (CsA) and tacrolimus (TAC) on colon anastomosis recovery. METHODS: Forty rats were randomly divided into 4 groups. The 4 groups were determined as follows: control group; sham group, given %0.09 NaCl; TAC group, given 0.5 mg/kg/day tacrolimus; and CsA group, given 5 mg/kg/day CsA. A 6-cm midabdomen incision was performed on the rats. An incision of all layers on the right colon was performed...
June 2017: Annals of Surgical Treatment and Research
Risa Yamazaki, Yoshitoshi Kasuya, Tetsuo Fujita, Hiroki Umezawa, Madoka Yanagihara, Hiroyuki Nakamura, Ichiro Yoshino, Koichiro Tatsumi, Toshihiko Murayama
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disorder that is characterized by aberrant tissue remodeling and the formation of fibroblastic foci that are composed of fibrogenic myofibroblasts. TGF-β1 is one of the factors that are responsible for fibrosis as it promotes fibroblast to myofibroblast differentiation (FMD) and is associated with up-regulation of α-smooth muscle actin. Therefore, inhibition of FMD may represent an effective strategy for the treatment of IPF. Here, we describe the treatment of human lung fibroblasts (WI-38 and HFL-1 cells) with cyclosporine A (CsA), which reduces TGF-β1-induced FMD via degradation of hypoxia-inducible factor-1α (HIF-1α)...
August 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Masachika Hayashi, Ami Aoki, Katsuaki Asakawa, Takuro Sakagami, Toshiaki Kikuchi, Toshinori Takada
A 59-year-old Japanese man diagnosed with interstitial lung disease associated with amyopathic dermatomyositis with anti-melanoma differentiation-associated gene 5 (MDA-5) antibodies was treated with intravenous methyl prednisolone (PSL) 1000 mg, oral PSL 1 mg/kg, and oral cyclosporin 200 mg daily. His respiratory condition worsened after treatment with two times of intravenous cyclophosphamide and another steroid pulse therapy as well as PSL and cyclosporin. Addition of mycophenolate mofetil (MMF), 1...
July 2017: Respirology Case Reports
S R Rao, R Subbarayan, D M Girija
Cyclosporine-A induces gingival overgrowth with disturbance in the homeostasis of cells and connective tissue proteins. Human gingival fibroblasts were cultured with cyclosporine A, and the expression of two vital endoplasmic stress markers and two prime matrix proteins (connective tissue growth factor (CTGF and periostin) were assessed by RT-PCR. We found that expression of Glucose-Regulated Protein 78 (GRP78/BIP) and CCAAT/enhancer binding protein, C/EBP homologous protein (CHOP) were significantly increased, along with CTGF and periostin, suggesting a role for these factors in gingival overgrowth...
January 2017: Journal of Biological Regulators and Homeostatic Agents
Suresh Ranga Rao, Shiyamali Sundararajan, Rajasekaran Subbarayan, Dinesh Murugan Girija
Cyclosporine-A (CsA) induces gingival overgrowth. Cyclosporine's anti-apoptotic activity in human gingival fibroblast is due to desensitization of mitochondrial permeability transition pore (MPTP) and augmentation of anti-apoptotic, Bcl2. Alternative mechanisms of apoptosis exist involving enzymes like calcium-dependent Calpain and signaling events related to apoptosis, like Glycogen synthase kinase 3β (GSK3β) and protein kinase A (PKA). Cyclosporine-A in renal tubular cells induces endoplasmic reticulum stress (ER stress) which has not been explored in gingival overgrowth...
May 2017: Molecular and Cellular Biochemistry
Ciprian Tomuleasa, Sonia Selicean, Grigore Gafencu, Bobe Petrushev, Laura Pop, Cristian Berce, Anca Jurj, Adrian Trifa, Ana-Maria Rosu, Sergiu Pasca, Lorand Magdo, Mihnea Zdrenghea, Delia Dima, Alina Tanase, Ioana Frinc, Anca Bojan, Ioana Berindan-Neagoe, Gabriel Ghiaur, Stefan O Ciurea
Although the cause for bone marrow fibrosis in patients with myelofibrosis remains controversial, it has been hypothesized that it is caused by extensive fibroblast proliferation under the influence of cytokines generated by the malignant megakaryocytes. Moreover, there is no known drug therapy which could reverse the process. We studied the fibroblasts in a novel system using the hanging drop method, evaluated whether the fibroblasts obtain from patients are part of the malignant clone of not and, using this system, we screen a large library of FDA-approved drugs to identify potential drugs candidates that might be useful in the treatment of this disease, specifically which would inhibit fibroblast proliferation and the development of bone marrow fibrosis...
January 2018: Journal of Cellular Physiology
Suresh Ranga Rao, Rajasekaran Subbarayan, Supraja Ajitkumar, Dinesh Murugan Girija
INTRODUCTION: Cyclosporin-A (CsA), an immunosuppressant, induces renal fibrosis and Renin Angiotensin System (RAS) is known to play a major role. CsA has the potential to increase the oxidative stress; specifically through the Advanced Oxidation Protein Products (AOPP) which could possibly stimulate fibrosis. A similar type of pathology occurs even in the gingiva known as CsA Induced Gingival Overgrowth (CIGO). AIM: This study was undertaken to estimate the AOPP generation by Human Gingival Fibroblasts (HGF) under the influence of CsA and Angiotensin II (Ang II)...
January 2017: Journal of Clinical and Diagnostic Research: JCDR
Yuting He, Ling Zhang, Zhuoli Zhu, Anqi Xiao, Haiyang Yu, Xueqi Gan
Glucocorticoids (GCs) are frequently used for the suppression of inflammation in chronic inflammatory diseases. Excessive GCs usage is greatly associated with several side effects, including gingival ulceration, the downward migration of the epithelium, attachment loss and disruption of transeptal fibers. The mechanisms underlying GCs-induced impairments in gingival tissue remains poorly understood. Mitochondrial dysfunction is associated with various oral diseases, such as chronic periodontitis, age-related alveolar bone loss and hydrogen peroxide-induced cell injury in gingival...
2017: PloS One
Taís Hanae Kasai-Brunswick, Andréa Rodrigues da Costa, Raiana Andrade Quintanilha Barbosa, Bruna Farjun, Fernanda Cristina Paccola Mesquita, Danúbia Silva Dos Santos, Isalira Peroba Ramos, Grazielle Suhett, Guilherme Visconde Brasil, Sandro Torrentes da Cunha, José Oscar R Brito, Juliana do Amaral Passipieri, Adriana Bastos Carvalho, Antonio Carlos Campos de Carvalho
BACKGROUND: Heart failure represents an important public health issue due to its high costs and growing incidence worldwide. Evidence showing the regenerative potential of postmitotic heart tissue has suggested the existence of endogenous cardiac stem cells in adult hearts. Cardiosphere-derived cells (CDC) constitute a candidate pool of such cardiac stem cells. Previous studies using acute myocardial infarction (MI) models in rodents demonstrated an improvement in cardiac function after cell therapy with CDC...
February 15, 2017: Stem Cell Research & Therapy
Suresh Ranga Rao, Rajasekaran Subbarayan, Supraja Ajitkumar, Dinesh Murugan Girija
Cyclosporine induces overgrowth of human gingiva. Previously we have shown (i) cyclosporine-inducing ER stress in human gingival fibroblasts (HGF), (ii) increased matrix protein expression, and (iii) interference with mitochondrial pro- and anti-apoptotic factors. This study was undertaken to assess the effects of melatonin (an antioxidant), 4PBA (an ER stress inhibitor), and simvastatin on the expression of ER Stress markers as well as on matrix and mitochondrial markers. HGF incubated with cyclosporine, or without melatonin/4PBA/statin...
January 2018: Journal of Cellular Physiology
Yeoun-Hee Kim, Jae-Chang Jung, Sang Il Gum, Su-Bin Park, Jin Yeul Ma, Yong Il Kim, Kyoo Won Lee, Young Jeung Park
We examined the connection between matrix metalloproteinase (MMP) expression/activity and pterygium fibroblast migration, and how these were affected by bevacizumab and/or cyclosporine A (CsA). Fibroblasts were obtained from 20 pterygia and 6 normal conjunctival specimens. Expression levels of MMP-3 and MMP-13 were examined after bevacizumab administration. Immunofluorescence staining was used to examine expression of both MMPs in fibroblasts migrating out from explanted pterygium tissues. Rates of cell migration from explant-cultured pterygia tissues and scratch-wounded confluent pterygium fibroblasts were examined in the presence of MMP-3 or MMP-13 inhibitors, as well as bevacizumab and/or CsA...
2017: PloS One
Sang Il Gum, Yeoun-Hee Kim, Jae-Chang Jung, Im Gyu Kim, Jun Seok Lee, Kyoo Won Lee, Young Jeung Park
Cyclosporine A (CsA), an immunomodulatory drug, and is increasingly used to treat moderate dry eye syndrome and ocular surface inflammation. However, any inhibitory effect on differentiation of fibroblasts to myofibroblasts remains unclear. Here, we show that the inhibitory effect of CsA on transforming growth factor-beta2 (TGF-β2)-induced myofibroblasts in primary cultured human pterygium fibroblasts. CsA significantly decreased mRNA and protein expression of myofibroblast-related markers including α-SMA, laminin, and fibronectin...
January 22, 2017: Biochemical and Biophysical Research Communications
Ajitkumar Supraja, Murugan Girija Dinesh, Subbarayan Rajasekaran, Thodur Madapusi Balaji, Suresh Ranga Rao
BACKGROUND: To evaluate the effect of Cyclosporin A (CsA) and angiotensin II (Ang II) on cytosolic calcium levels in cultured human gingival fibroblasts (HGFs). MATERIALS AND METHODS: Healthy gingival samples from six volunteers were obtained, and primary HGFs were cultured. Cell viability and proliferation assay were performed to identify the ideal concentrations of CsA and Ang II. Cytosolic calcium levels in cultured gingival fibroblasts treated with CsA and Ang II were studied using colorimetric assay, confocal and fluorescence imaging...
September 2016: Dental Research Journal
Mark Hanudel, Harald Jüppner, Isidro B Salusky
In chronic kidney disease, systemic inflammation is common and associated with mortality. The present study demonstrates that fibroblast growth factor 23 (FGF23) contributes to uremic inflammation by increasing hepatic expression and secretion of inflammatory cytokines. FGF23 binds to hepatic FGFR4, inducing calcineurin/nuclear factor of activated T-cell signaling, resulting in increased expression of interleukin 6 and C-reactive protein. The proinflammatory effects of FGF23 are inhibited by an isoform-specific FGFR4 blocking antibody and by cyclosporine, a calcineurin inhibitor...
November 2016: Kidney International
Niina K Palin, Johanna Savikko, Arja Pasternack, Jukka M Rintala, Bhanu Kalra, Shivani Mistry, Ajay Kumar, Marie-Paule Roth, Heikki Helin, Olli Ritvos
Activins are members of the transforming growth factor-beta (TGF-β) superfamily of cytokines. They play critical roles in the onset of acute and chronic inflammatory responses. The aim of this study was to investigate how activin inhibition affects acute kidney injury and inflammation after transplantation. The study was carried out in kidney transplantation and renal ischemia-reperfusion models in the rat. Soluble activin type 2 receptor (sActRIIB-Fc) was used to inhibit activin signaling. Transplantation groups were as follows: (i) cyclosporine A (CsA) (ii) CsA + sActRIIB-Fc, (iii) CsA+ inactive protein control Fc-G1...
January 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
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