Spontaneous hepatic fibrosis in transgenic mice overexpressing PDGF-A

Thieringer, F.; Maass, T; Czochra, P.; Klopcic, Borut; Conrad, I.; Friebe, D.; Schirmacher, Peter; Lohse, Ansgar W.; Blessing, Manfred; Galle, Peter R.; Teufel, Andreas; Kanzler, Stephan

doi:10.1016/j.gene.2008.05.022

Cited by 52 publications

(44 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Consistently, adenovirally induced overexpression of PDGF-BB also resulted in mild pulmonary fibrosis (15). Overexpression of PDGF-A or PDGF-B chains in organs other than the lungs resulted in tissue fibrosis as well (16).…”

Section: Pdgf and Pdgfr In Sscmentioning

confidence: 80%

Stimulatory autoantibodies to platelet‐derived growth factor receptors in systemic sclerosis: What functional autoimmunity could learn from receptor biology

Dragun¹,

Distler²,

Riemekasten³

et al. 2009

Arthritis & Rheumatism

View full text Add to dashboard Cite

Section: Pdgf and Pdgfr In Sscmentioning

confidence: 80%

Stimulatory autoantibodies to platelet‐derived growth factor receptors in systemic sclerosis: What functional autoimmunity could learn from receptor biology

Dragun¹,

Distler²,

Riemekasten³

et al. 2009

Arthritis & Rheumatism

View full text Add to dashboard Cite

“…Although previous studies have not described PDGFA mRNA levels in platelets, Thieringer et al 10 demonstrated that PDGFA mRNA expression was associated with increased TGFB1 protein expression in hepatic tissue from transgenic mice, suggesting a profibrogenic role for PDGFA via induction of the TGFB1 signaling pathway.…”

Section: Ethical Considerationsmentioning

confidence: 94%

“…There are four different PDGF isoforms 8 and the PDGFB isoform is considered the most important mitogen for HSCs [7][8][9] . However, studies have demonstrated that PDGFA can also be considered an important profibrogenic agent, acting via TGFB1 induction 10 .…”

mentioning

confidence: 99%

Platelet-derived growth factor A mRNA in platelets is associated with the degree of hepatic fibrosis in chronic hepatitis C

Tanikawa

Grotto

Silva

et al. 2017

Rev. Soc. Bras. Med. Trop.

View full text Add to dashboard Cite

Abstract:Introduction: Transforming growth factor beta 1 (TGFB1) and platelet-derived growth factor (PDGF) are the main cytokines related to hepatic fibrogenesis. Methods: RNA isolated from the platelets and hepatic tissue of 43 HCV carriers was used for quantitative polymerase chain reaction to determine TGFB1, PDGFA, and PDGFB RNA expression. Results: The mRNA expression of PDGFA in platelets was significantly lower in the group with advanced fibrosis than in the group with earlystage fibrosis. TGFB1 was more frequently expressed in platelets than in hepatic tissue, which was different from PDGFB. Conclusions: A pathway mediated by overexpression of TGFB1 via PDGFA in megakaryocytes could be involved in the development of fibrosis.Keywords: Hepatic fibrosis. PDGF. TGFB.Hepatic fibrosis, a consequence of various chronic stimuli, including infection with hepatitis C virus (HCV), is characterized by the progressive accumulation of extracellular matrix (ECM) components in the hepatic parenchyma, which leads to a progressive replacement of the functional tissue with scar tissue 1 .Hepatic stellate cells (HSCs) are considered the main cells producing ECM proteins 2 and their activation and proliferation are mediated by two cytokines, transforming growth factor beta 1 (TGFB1) and platelet-derived growth factor (PDGF). Both are secreted by HSCs, platelets, and other cells 3,4 .Transforming growth factor beta 1 is the major profibrogenic cytokine in the liver because of its contribution to fibrosis development via HSC activation and the regulation of gene expression associated with signaling cascades related to fibrosis 5,6 . Platelet-derived growth factor is the most potent mitogen for HSCs 7 . There are four different PDGF isoforms 8 and the PDGFB isoform is considered the most important mitogen for HSCs [7][8][9] . However, studies have demonstrated that PDGFA can also be considered an important profibrogenic agent, acting via TGFB1 induction 10 .Considering that platelets are major sources of TGFB1 and PDGF, which are growth factors involved in the development of liver fibrosis associated with chronic hepatitis C, and that studies have already demonstrated that platelets that accumulate in the liver during chronic hepatitis may be involved in hepatic fibrosis 11 , the aim of this study was to evaluate the expressions of PDGFA, PDGFB, and TGFB1 in hepatic tissue and platelets from HCV-infected patients presenting with varying degrees of hepatic fibrosis.Aliquots of ethylenediaminetetraacetic acid (EDTA)-anticoagulated peripheral venous blood and fragments of hepatic tissue were collected from 43 HCV-infected patients who presented at the Department of Internal Medicine, Gastroenterology Division, Botucatu Medical School, São Paulo State University [Universidade Estadual Paulista (UNESP)], Botucatu, SP, Brazil. The inclusion criteria were naïve patients infected with HCV genotype 1 who were aged >18 years, had undergone a liver biopsy before the start of antiviral treatment, and had signed informed consent. The exclu...

show abstract

“…In support of a role for PDGF-B in the development of liver fibrosis, transgenic overexpression of PDGF-B stimulates development of liver fibrosis [8]. Similarly, transgenic expression of PDGF-A in mice promotes liver fibrosis [9]. Compared to PDGF-B, however, PDGF-A is far less potent at simulating HSC proliferation in vitro.…”

Section: Mediators That Stimulate Hsc Proliferationmentioning

confidence: 99%

Phenotypic Changes in Hepatic Stellate Cells in Response to Toxic Liver Injury

Copple

2014

Curr Pathobiol Rep

View full text Add to dashboard Cite

Hepatic stellate cells (HSCs) are the main extracellular matrix-producing cell type in the liver. These cells exist in a quiescent state in normal liver and an activated state in damaged liver. During quiescence, HSCs store and release various retinoids. After injury to the liver, however, various protein and non-protein mediators are released from cells that stimulate HSCs to differentiate into myofibroblasts, a process termed activation. Activated HSCs begin to express a-smooth muscle actin and migrate to sites of injury through chemotaxis. Within the damaged region of liver, these cells become contractile and produce growth factors that promote hepatocyte replication and angiogenesis, produce extracellular matrix that forms the scaffold for liver repair, and produce proteins that modulate immune cell function. Once liver repair is complete and liver function is restored, HSCs revert back to a quiescent phenotype or die by apoptosis. If liver injury becomes chronic, however, these processes persist resulting in the formation of an extensive scar (i.e., fibrosis) that ultimately leads to liver failure. Because of the importance of these cells to the development of liver fibrosis, there has been extensive research into understanding the mechanisms that drive HSC activation after injury and the mechanisms that regulate reversion of these cells back to quiescence after resolution of injury. In addition, there has been great interest in identifying the various functions of HSCs after acute and chronic injury. The aim of this review is to briefly discuss the phenotypic changes that occur in HSCs after acute and chronic liver injury and to highlight some of the important functions of these cells during repair of the liver.

show abstract

Spontaneous hepatic fibrosis in transgenic mice overexpressing PDGF-A

Cited by 52 publications

References 37 publications

Stimulatory autoantibodies to platelet‐derived growth factor receptors in systemic sclerosis: What functional autoimmunity could learn from receptor biology

Stimulatory autoantibodies to platelet‐derived growth factor receptors in systemic sclerosis: What functional autoimmunity could learn from receptor biology

Platelet-derived growth factor A mRNA in platelets is associated with the degree of hepatic fibrosis in chronic hepatitis C

Phenotypic Changes in Hepatic Stellate Cells in Response to Toxic Liver Injury

Contact Info

Product

Resources

About