کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8455025 | 1547994 | 2018 | 45 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Liver fibrosis: Direct antifibrotic agents and targeted therapies
ترجمه فارسی عنوان
فیبروز کبدی: عوامل ضد انعقادی مستقیم و درمان های هدفمند
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کلمات کلیدی
ECMDDR1TGFFAPPDGFASOTG2CholangiocyteDDRLOXLCrosslinkNAFLDMMPHSCDdr2 - Dr2antisense oligonucleotide - oligonucleotide antisenseSmall interfering RNA - RNA تداخل کوچکsiRNA - siRNAnonalcoholic steatohepatitis - استاتو هپاتیت غیر الکلیLOX - اکسیژن مایعIntegrin - اینتگرینNonalcoholic fatty liver disease - بیماری کبدی چربی غیر الکلیBiomarker - بیومارکرtransforming growth factor - تبدیل فاکتور رشدTransglutaminase - ترانس گلوتامینازTransglutaminase 2 - ترانس گلوتامیناز 2TIMP - زمانHepatic stellate cell(s) - سلولهای ستون فقرات کبدیCytokine - سیتوکینCirrhosis - سیروزAntifibrotic - ضد عفونی کنندهplatelet derived growth factor - فاکتور رشد حاصل از پلاکتFibroblast - فیبروبلاستFibrosis - فیبروز یا فساد الیافLysyl oxidase - لیسییل اکسیدازExtracellular matrix - ماتریکس خارج سلولیmatrix metalloproteinase - ماتریکس متالوپروتئینازTissue inhibitor of metalloproteinases - مهار کننده های متالوپروتئینازهای بافتNash - نوشFibroblast activation protein - پروتئین فعال سازی فیبربلاستLiver - کبدCollagen - کلاژنDiscoidin domain receptor - گیرنده دامنه دیسکوید
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
چکیده انگلیسی
Liver fibrosis and in particular cirrhosis are the major causes of morbidity and mortality of patients with chronic liver disease. Their prevention or reversal have become major endpoints in clinical trials with novel liver specific drugs. Remarkable progress has been made with therapies that efficiently address the cause of the underlying liver disease, as in chronic hepatitis B and C. Highly effective antiviral therapy can prevent progression or even induce reversal in the majority of patients, but such treatment remains elusive for the majority of liver patients with advanced alcoholic or nonalcoholic steatohepatitis, genetic or autoimmune liver diseases. Moreover, drugs that would speed up fibrosis reversal are needed for patients with cirrhosis, since even with effective causal therapy reversal is slow or the disease may further progress. Therefore, highly efficient and specific antifibrotic agents are needed that can address advanced fibrosis, i.e., the detrimental downstream result of all chronic liver diseases. This review discusses targeted antifibrotic therapies that address molecules and mechanisms that are central to fibrogenesis or fibrolysis, including strategies that allow targeting of activated hepatic stellate cells and myofibroblasts and other fibrogenic effector cells. Focus is on collagen synthesis, integrins and cells and mechanisms specific including specific downregulation of TGFbeta signaling, major extracellular matrix (ECM) components, ECM-crosslinking, and ECM-receptors such as integrins and discoidin domain receptors, ECM-crosslinking and methods for targeted delivery of small interfering RNA, antisense oligonucleotides and small molecules to increase potency and reduce side effects. With an increased understanding of the biology of the ECM and liver fibrosis and an improved preclinical validation, the translation of these approaches to the clinic is currently ongoing. Application to patients with liver fibrosis and a personalized treatment is tightly linked to the development of noninvasive biomarkers of fibrosis, fibrogenesis and fibrolysis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Matrix Biology - Volumes 68â69, August 2018, Pages 435-451
Journal: Matrix Biology - Volumes 68â69, August 2018, Pages 435-451
نویسندگان
Detlef Schuppan, Muhammad Ashfaq-Khan, Ai Ting Yang, Yong Ook Kim,