Fibrogenesis & Tissue Repair最新文献_第8页

Interventions in Wnt signaling as a novel therapeutic approach to improve myocardial infarct healing. 干预Wnt信号作为一种改善心肌梗死愈合的新治疗方法。

Fibrogenesis & Tissue Repair Pub Date : 2012-09-11 DOI: 10.1186/1755-1536-5-16

Kevin Cm Hermans, Evangelos P Daskalopoulos, W Matthijs Blankesteijn

{"title":"Interventions in Wnt signaling as a novel therapeutic approach to improve myocardial infarct healing.","authors":"Kevin Cm Hermans, Evangelos P Daskalopoulos, W Matthijs Blankesteijn","doi":"10.1186/1755-1536-5-16","DOIUrl":"https://doi.org/10.1186/1755-1536-5-16","url":null,"abstract":" Following myocardial infarction, wound healing takes place in the infarct area where the non-viable cardiac tissue is replaced by a scar. Inadequate wound healing or insufficient maintenance of the extracellular matrix in the scar can lead to excessive dilatation of the ventricles, one of the hallmarks of congestive heart failure. Therefore, it is important to better understand the wound-healing process in the heart and to develop new therapeutic agents that target the infarct area in order to maintain an adequate cardiac function. One of these potential novel therapeutic targets is Wnt signaling. Wnt signaling plays an important role in embryonic myocardial development but in the adult heart the pathway is thought to be silent. However, there is increasing evidence that components of the Wnt pathway are re-expressed during cardiac repair, implying a regulatory role. Recently, several studies have been published where the effect of interventions in Wnt signaling on infarct healing has been studied. In this review, we will summarize the results of these studies and discuss the effects of these interventions on the different cell types that are involved in the wound healing process.","PeriodicalId":12264,"journal":{"name":"Fibrogenesis & Tissue Repair","volume":"5 1","pages":"16"},"PeriodicalIF":0.0,"publicationDate":"2012-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1755-1536-5-16","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30896845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 33

Cardiac fibroblasts, fibrosis and extracellular matrix remodeling in heart disease. 心脏病中的心脏成纤维细胞、纤维化和细胞外基质重塑。

Fibrogenesis & Tissue Repair Pub Date : 2012-09-03 DOI: 10.1186/1755-1536-5-15

Dong Fan, Abhijit Takawale, Jiwon Lee, Zamaneh Kassiri

{"title":"Cardiac fibroblasts, fibrosis and extracellular matrix remodeling in heart disease.","authors":"Dong Fan, Abhijit Takawale, Jiwon Lee, Zamaneh Kassiri","doi":"10.1186/1755-1536-5-15","DOIUrl":"https://doi.org/10.1186/1755-1536-5-15","url":null,"abstract":" Fibroblasts comprise the largest cell population in the myocardium. In heart disease, the number of fibroblasts is increased either by replication of the resident myocardial fibroblasts, migration and transformation of circulating bone marrow cells, or by transformation of endothelial/epithelial cells into fibroblasts and myofibroblasts. The primary function of fibroblasts is to produce structural proteins that comprise the extracellular matrix (ECM). This can be a constructive process; however, hyperactivity of cardiac fibroblasts can result in excess production and deposition of ECM proteins in the myocardium, known as fibrosis, with adverse effects on cardiac structure and function. In addition to being the primary source of ECM proteins, fibroblasts produce a number of cytokines, peptides, and enzymes among which matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitor of metalloproteinases (TIMPs), directly impact the ECM turnover and homeostasis. Function of fibroblasts can also in turn be regulated by MMPs and TIMPs. In this review article, we will focus on the function of cardiac fibroblasts in the context of ECM formation, homeostasis and remodeling in the heart. We will discuss the origins and multiple roles of cardiac fibroblasts in myocardial remodeling in different types of heart disease in patients and in animal models. We will further provide an overview of what we have learned from experimental animal models and genetically modified mice with altered expression of ECM regulatory proteins, MMPs and TIMPs.","PeriodicalId":12264,"journal":{"name":"Fibrogenesis & Tissue Repair","volume":"5 1","pages":"15"},"PeriodicalIF":0.0,"publicationDate":"2012-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1755-1536-5-15","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30877956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 685

Cardiac myofibroblasts: cells out of balance. A new thematic series. 心肌成纤维细胞:细胞失衡。一个新的专题系列。

Fibrogenesis & Tissue Repair Pub Date : 2012-09-03 DOI: 10.1186/1755-1536-5-14

Ian M C Dixon

引用次数: 7

Diabetic angiopathy and angiogenic defects. 糖尿病血管病变和血管生成缺陷。

Fibrogenesis & Tissue Repair Pub Date : 2012-08-01 DOI: 10.1186/1755-1536-5-13

Ling Xu, Keizo Kanasaki, Munehiro Kitada, Daisuke Koya

引用次数: 49

Induction of microRNA-214-5p in human and rodent liver fibrosis. microRNA-214-5p在人和啮齿动物肝纤维化中的诱导作用。

Fibrogenesis & Tissue Repair Pub Date : 2012-08-01 DOI: 10.1186/1755-1536-5-12

Masashi Iizuka, Tomohiro Ogawa, Masaru Enomoto, Hiroyuki Motoyama, Katsutoshi Yoshizato, Kazuo Ikeda, Norifumi Kawada

{"title":"Induction of microRNA-214-5p in human and rodent liver fibrosis.","authors":"Masashi Iizuka, Tomohiro Ogawa, Masaru Enomoto, Hiroyuki Motoyama, Katsutoshi Yoshizato, Kazuo Ikeda, Norifumi Kawada","doi":"10.1186/1755-1536-5-12","DOIUrl":"https://doi.org/10.1186/1755-1536-5-12","url":null,"abstract":"Background: miRNAs are non-coding RNAs that regulate gene expression in a wide range of biological contexts, including a variety of diseases. The present study clarified the role of miR-214-5p in hepatic fibrogenesis using human clinical tissue samples, livers from rodent models, and cultured hepatic stellate cells.Methods: The expression of miR-214-5p and genes that are involved in liver fibrosis were analyzed in hepatitis C virus-infected human livers, rodent fibrotic livers, a human stellate cell line (LX-2), and the cells from intact mouse livers using real-time PCR. The effect of miR-214-5p overexpression in LX-2 cells on cell function was investigated. Twist-1 expression in the liver tissues of mouse models and primary-cultured stellate cells was also analyzed.Results: miR-214-5p was upregulated in human and mouse livers in a fibrosis progression-dependent manner. miR-214-5p expression increased during the culture-dependent activation of mouse primary stellate cells and was significantly higher in stellate cells than in hepatocytes. The overexpression of miR-214-5p in LX-2 cells increased the expression of fibrosis-related genes, such as matrix metalloproteinase (MMP)-2, MMP-9, α-smooth muscle actin, and transforming growth factor (TGF)-β1. TGF-β stimulation induced miR-214-5p in LX-2 cells. Twist-1 was increased in fibrotic mouse livers and induced during mouse stellate cell activation.Conclusion: miR-214-5p may play crucial roles in the activation of stellate cells and the progression of liver fibrosis. Twist-1 may regulate miR-214-5p expression in the liver, particularly in stellate cells.","PeriodicalId":12264,"journal":{"name":"Fibrogenesis & Tissue Repair","volume":"5 1","pages":"12"},"PeriodicalIF":0.0,"publicationDate":"2012-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1755-1536-5-12","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30801045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 76

Molecular and cellular mechanisms of pulmonary fibrosis. 肺纤维化的分子和细胞机制。

Fibrogenesis & Tissue Repair Pub Date : 2012-07-23 DOI: 10.1186/1755-1536-5-11

Nevins W Todd, Irina G Luzina, Sergei P Atamas

引用次数: 326

Augmenter of liver regeneration. 肝脏再生增强剂。

Fibrogenesis & Tissue Repair Pub Date : 2012-07-09 DOI: 10.1186/1755-1536-5-10

Chandrashekhar R Gandhi

{"title":"Augmenter of liver regeneration.","authors":"Chandrashekhar R Gandhi","doi":"10.1186/1755-1536-5-10","DOIUrl":"https://doi.org/10.1186/1755-1536-5-10","url":null,"abstract":" 'Augmenter of liver regeneration' (ALR) (also known as hepatic stimulatory substance or hepatopoietin) was originally found to promote growth of hepatocytes in the regenerating or injured liver. ALR is expressed ubiquitously in all organs, and exclusively in hepatocytes in the liver. ALR, a survival factor for hepatocytes, exhibits significant homology with ERV1 (essential for respiration and viability) protein that is essential for the survival of the yeast, Saccharomyces cerevisiae. ALR comprises 198 to 205 amino acids (approximately 22 kDa), but is post-translationally modified to three high molecular weight species (approximately 38 to 42 kDa) found in hepatocytes. ALR is present in mitochondria, cytosol, endoplasmic reticulum, and nucleus. Mitochondrial ALR may be involved in oxidative phosphorylation, but also functions as sulfhydryl oxidase and cytochrome c reductase, and causes Fe/S maturation of proteins. ALR, secreted by hepatocytes, stimulates synthesis of TNF-α, IL-6, and nitric oxide in Kupffer cells via a G-protein coupled receptor. While the 22 kDa rat recombinant ALR does not stimulate DNA synthesis in hepatocytes, the short form (15 kDa) of human recombinant ALR was reported to be equipotent as or even stronger than TGF-α or HGF as a mitogen for hepatocytes. Altered serum ALR levels in certain pathological conditions suggest that it may be a diagnostic marker for liver injury/disease. Although ALR appears to have multiple functions, the knowledge of its role in various organs, including the liver, is extremely inadequate, and it is not known whether different ALR species have distinct functions. Future research should provide better understanding of the expression and functions of this enigmatic molecule.","PeriodicalId":12264,"journal":{"name":"Fibrogenesis & Tissue Repair","volume":"5 1","pages":"10"},"PeriodicalIF":0.0,"publicationDate":"2012-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1755-1536-5-10","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30748277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 59

Mechanical stretch up-regulates the B-type natriuretic peptide system in human cardiac fibroblasts: a possible defense against transforming growth factor-β mediated fibrosis. 机械拉伸上调人心脏成纤维细胞b型利钠肽系统:对转化生长因子-β介导的纤维化的可能防御。

Fibrogenesis & Tissue Repair Pub Date : 2012-07-07 DOI: 10.1186/1755-1536-5-9

Chris J Watson, Dermot Phelan, Maojia Xu, Patrick Collier, Roisin Neary, Albert Smolenski, Mark Ledwidge, Kenneth McDonald, John Baugh

{"title":"Mechanical stretch up-regulates the B-type natriuretic peptide system in human cardiac fibroblasts: a possible defense against transforming growth factor-β mediated fibrosis.","authors":"Chris J Watson, Dermot Phelan, Maojia Xu, Patrick Collier, Roisin Neary, Albert Smolenski, Mark Ledwidge, Kenneth McDonald, John Baugh","doi":"10.1186/1755-1536-5-9","DOIUrl":"https://doi.org/10.1186/1755-1536-5-9","url":null,"abstract":"Background: Mechanical overload of the heart is associated with excessive deposition of extracellular matrix proteins and the development of cardiac fibrosis. This can result in reduced ventricular compliance, diastolic dysfunction, and heart failure. Extracellular matrix synthesis is regulated primarily by cardiac fibroblasts, more specifically, the active myofibroblast. The influence of mechanical stretch on human cardiac fibroblasts' response to pro-fibrotic stimuli, such as transforming growth factor beta (TGFβ), is unknown as is the impact of stretch on B-type natriuretic peptide (BNP) and natriuretic peptide receptor A (NPRA) expression. BNP, acting via NPRA, has been shown to play a role in modulation of cardiac fibrosis.Methods and results: The effect of cyclical mechanical stretch on TGFβ induction of myofibroblast differentiation in primary human cardiac fibroblasts and whether differences in response to stretch were associated with changes in the natriuretic peptide system were investigated. Cyclical mechanical stretch attenuated the effectiveness of TGFβ in inducing myofibroblast differentiation. This finding was associated with a novel observation that mechanical stretch can increase BNP and NPRA expression in human cardiac fibroblasts, which could have important implications in modulating myocardial fibrosis. Exogenous BNP treatment further reduced the potency of TGFβ on mechanically stretched fibroblasts.Conclusion: We postulate that stretch induced up-regulation of the natriuretic peptide system may contribute to the observed reduction in myofibroblast differentiation.","PeriodicalId":12264,"journal":{"name":"Fibrogenesis & Tissue Repair","volume":"5 1","pages":"9"},"PeriodicalIF":0.0,"publicationDate":"2012-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1755-1536-5-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30743609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 50

Replacement of hematopoietic system by allogeneic stem cell transplantation in myelofibrosis patients induces rapid regression of bone marrow fibrosis. 骨髓纤维化患者用同种异体干细胞移植替代造血系统可诱导骨髓纤维化快速消退。

Fibrogenesis & Tissue Repair Pub Date : 2012-06-06 eCollection Date: 2012-01-01 DOI: 10.1186/1755-1536-5-S1-S25

Nicolaus Kröger, Michael Kvasnicka, Jürgen Thiele

{"title":"Replacement of hematopoietic system by allogeneic stem cell transplantation in myelofibrosis patients induces rapid regression of bone marrow fibrosis.","authors":"Nicolaus Kröger, Michael Kvasnicka, Jürgen Thiele","doi":"10.1186/1755-1536-5-S1-S25","DOIUrl":"https://doi.org/10.1186/1755-1536-5-S1-S25","url":null,"abstract":"Bone marrow fibrosis is a hallmark of primary and post ET/PV myelofibrosis. To investigated the impact of replacement of the hematopoietic system in myelofibrosis patients by allogeneic stem cell transplantation on bone marrow fibrosis, we studied bone marrow fibrosis on bone marrow samples from 24 patients with myelofibrosis before and after dose-reduced conditioning followed by allogeneic stem cell transplantation from related or unrelated donor. Using the European Consensus on Grading Bone Marrow Fibrosis, before allografting all patients had advanced fibrosis MF-2 (n = 13) or MF-3 (n = 11). After transplantation, a complete (MF-0) or nearly complete (MF-1) regression of bone marrow fibrosis was seen in 59 % at day +100, in 90 % at day +180, and in 100 % at day +360. No correlation between occurrence of acute graft-versus-host disease, and fibrosis regression on day +180 was seen. We conclude that dose-reduced conditioning, followed by allogeneic stem cell transplantation, resulted in a rapid resolution of bone-marrow fibrosis suggesting the bone marrow fibrogenesis is a highly dynamic rather than static process in patients with myelofibrosis. ","PeriodicalId":12264,"journal":{"name":"Fibrogenesis & Tissue Repair","volume":"5 Suppl 1","pages":"S25"},"PeriodicalIF":0.0,"publicationDate":"2012-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1755-1536-5-S1-S25","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31139344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 18

Fibrocytes in health and disease. 健康和疾病中的纤维细胞。

Fibrogenesis & Tissue Repair Pub Date : 2012-06-06 eCollection Date: 2012-01-01 DOI: 10.1186/1755-1536-5-S1-S6

Adriana Blakaj, Richard Bucala

引用次数: 11