Increased expression of plasminogen activator and plasminogen activator inhibitor during liver fibrogenesis of rats: role of stellate cells

Zhang, Li Ping; Takahara, Taro; Yata, Yutaka; Furui, Kei; Jin, Bo; Kawada, Norifumi; Watanabe, Akïharu

doi:10.1016/s0168-8278(99)80351-1

Cited by 117 publications

(112 citation statements)

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“…181 Stellate cells express uroplasminogen activator receptor and its inhibitor, as well as other components of the plasmin system. [182][183][184] Collectively, these findings suggest that stellate cells contain most, if not all, of the molecules necessary to either activate or inhibit metalloproteinases.…”

Section: Matrix Degradation and Resolution Of Fibrosismentioning

confidence: 91%

Mechanisms of Hepatic Fibrogenesis

2008

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Substantial improvements in the treatment of chronic liver disease have accelerated interest in uncovering the mechanisms underlying hepatic fibrosis and its resolution. Activation of resident hepatic stellate cells into proliferative, contractile, and fibrogenic cells in liver injury remains a dominant theme driving the field. However, several new areas of rapid progress in the past 5-10 years also have taken root, including: (1) identification of different fibrogenic populations apart from resident stellate cells, for example, portal fibroblasts, fibrocytes, and bone-marrow-derived cells, as well as cells derived from epithelial mesenchymal transition; (2) emergence of stellate cells as finely regulated determinants of hepatic inflammation and immunity; (3) elucidation of multiple pathways controlling gene expression during stellate cell activation including transcriptional, posttranscriptional, and epigenetic mechanisms; (4) recognition of disease-specific pathways of fibrogenesis; (5) re-emergence of hepatic macrophages as determinants of matrix degradation in fibrosis resolution and the importance of matrix cross-linking and scar maturation in determining reversibility; and (6) hints that hepatic stellate cells may contribute to hepatic stem cell behavior, cancer, and regeneration. Clinical and translational implications of these advances have become clear, and have begun to impact significantly on the management and outlook of patients with chronic liver disease.The field of hepatic fibrosis is flourishing thanks to continued experimental advances complemented by exciting progress in the treatment of chronic liver disease. 1 Control of chronic hepatitis B and C by antiviral therapies has established that advanced fibrosis can regress in association with improved clinical outcomes, 2-4 thereby intensifying enthusiasm to uncover the mechanistic basis for hepatic fibrogenesis and its attenuation. At the same time, simple paradigms defining the cellular sources of extracellular matrix (ECM), and the roles of cytokines and paracrine interactions among resident liver cells and inflammatory cells have yielded a more nuanced understanding of how the liver responds to injury. These advances have had a collateral benefit towards understanding fibrosis in other organs, particularly the pancreas. 5 Thus, a review of the mechanisms underlying hepatic fibrosis is not only timely, but is more clinically relevant than ever. This article focuses on recent advances in the field, building on established principles from earlier reviews 6,7 while weaving in their clinical relevance, but also emphasizing the molecular subtleties that have emerged through continued progress in the field. General PrinciplesFibrosis, or scarring of the liver, is a wound-healing response that engages a range of cell types and mediators to encapsulate injury. Although even acute injury will activate mechanisms of fibrogenesis, the sustained signals associated with chronic liver disease caused by infection, Cirrhosis, the most advanced stage ...

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Section: Matrix Degradation and Resolution Of Fibrosismentioning

confidence: 91%

Mechanisms of Hepatic Fibrogenesis

2008

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“…Zhang et al [15] reported that increased uPA and uPAR may act on matrix degradation in the early fibrotic liver. uPAR and tPA were associated with overall inhibition of matrix degradation in advanced cirrhotic liver.…”

Section: Group (N) Upa (Ng/l) Pai-1 (Ng/l)mentioning

confidence: 99%

Effects of the Traditional Chinese Medicine Dilong on Airway Remodeling in Rats with OVA-induced-Asthma

et al. 2016

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The present study focuses on the effects and suggests possible mechanisms of the traditional Chinese medicine Dilong as compared to dexamethasone on lower respiratory tract remodeling in rats with asthma. The number of leukocytes and eosinophils in blood from the inferior vena cava and bronchoalveolar lavage fluid (BALF) were counted. Lung tissues underwent hematoxylin and eosin staining. The thickness of the basement membrane and smooth muscle or the airways, and the ratio of inner to outer diameter of the airway wall were measured. Levels of transforming growth factor β1 (TGF-β1), matrix metallopeptidase 9/tissue inhibitor of metalloproteinase 1 (MMP-9/TIMP-1), urokinase plasminogen activator (uPA), plasminogen activator inhibitor 1 (PAI-1), and c-Myc(mRNA) were evaluated. Results indicate that treatment with Dilong decreased the number of eosinophils in blood and BALF, decreased levels of TGF-β1, MMP-9/TIMP-1, uPA, PAI-1 and c-Myc, and ameliorated the thickening of airway walls, airway basement membrane and airway smooth muscle. Co-treatment with dexamethasone was found to intensity these effects. The cellularity of eosinophils and thickness of the airway basement membrane and smooth muscle were positively correlated with levels of TGF- 1, uPA, and c-Myc. Treatment with Dilong, either alone or in combination with dexamethasone, could inhibit and partly reverse airway remodeling in rats with asthma at an early stage.

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“…Transforming growth factor beta (TGFβ) is known to be one of the most potent profibrogenic cytokines (Poli, 2000). Plasminogen activator inhibitor -1 (Pai-1) mainly regulates fibrinolysis by inhibiting plasminogen activator, but it was shown in several animal models that Pai-1 also contributes to hepatic fibrosis while Pai-1 deficiency protects against ECM accumulation (Bergheim et al, 2006,Wang et al, 2007,Zhang et al, 1999.…”

Section: Iii24 Mrna Expression Of Markers Of Hepatic Inflammationmentioning

confidence: 99%