Mechanisms by which acute phase proteins enhance development of liver fibrosis: Effects on collagenase and prolyl-4-hydroxylase activity in the rat liver

Gool, J. van; Nie, I. de; Smit, J.; Zuyderhoudt, F. M. J.

doi:10.1016/0014-4800(86)90056-0

Cited by 17 publications

(7 citation statements)

References 20 publications

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“…Genes encoding adhesion proteins and related mediators of chemotaxis were differentially expressed in response to fibrogenic chemicals, including Itgal (Huang and Brigstock, 2011); Fbn1 (Dubuisson et al, 2001;Lorena et al, 2004); Lamac2 and its regulator Lcn2 (Ngal), a marker of inflammatory injury and chemotaxis in multiple model systems (Brenner, 2009;Kim et al, 2010;Leung et al, 2012;Seki and Brenner, 2008); and Vim, encoding the inflammatory protein VIM (Vassiliadis et al, 2012). Acute phase proteins associated with hepatotoxicity in animal models include C1qb, encoding complement component (Cao et al, 2001); Cp, encoding the copper-binding ceruloplasmin (negatively correlated with hepatitis B-induced cirrhosis (van Gool et al, 1986); Gpnmb, encoding the protein involved in upregulation of restorative macrophages but not profibrotic macrophages (Li et al, 2010); genes encoding the neutrophil-associated chemokines Cxcl1, Cxcl16, and Ccl2 (Wald et al, 2004;Xu et al, 2004); Cd9 and Cd53, genes encoding tetraspanin family members associated with hepatic stellate cell migration (Mazzocca et al, 2002;Pinzani and Rombouts, 2004); and the gene encoding the antifibrinolytic protease inhibitor A2m. Plasma protein concentration of A2M is currently part of the FibroSure diagnostic panel used clinically to diagnose steatosis and fibrosis (Rossi et al, 2003).…”

Section: Gene Signatures In Hepatotoxic Injurymentioning

confidence: 99%

Gene Expression Patterns Associated With Histopathology in Toxic Liver Fibrosis

et al. 2015

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Toxic industrial chemicals induce liver injury, which is difficult to diagnose without invasive procedures. Identifying indicators of end organ injury can complement exposure-based assays and improve predictive power. A multiplexed approach was used to experimentally evaluate a panel of 67 genes predicted to be associated with the fibrosis pathology by computationally mining DrugMatrix, a publicly available repository of gene microarray data. Five-day oral gavage studies in male Sprague Dawley rats dosed with varying concentrations of 3 fibrogenic compounds (allyl alcohol, carbon tetrachloride, and 4,4'-methylenedianiline) and 2 nonfibrogenic compounds (bromobenzene and dexamethasone) were conducted. Fibrosis was definitively diagnosed by histopathology. The 67-plex gene panel accurately diagnosed fibrosis in both microarray and multiplexed-gene expression assays. Necrosis and inflammatory infiltration were comorbid with fibrosis. ANOVA with contrasts identified that 51 of the 67 predicted genes were significantly associated with the fibrosis phenotype, with 24 of these specific to fibrosis alone. The protein product of the gene most strongly correlated with the fibrosis phenotype PCOLCE (Procollagen C-Endopeptidase Enhancer) was dose-dependently elevated in plasma from animals administered fibrogenic chemicals (P < .05). Semiquantitative global mass spectrometry analysis of the plasma identified an additional 5 protein products of the gene panel which increased after fibrogenic toxicant administration: fibronectin, ceruloplasmin, vitronectin, insulin-like growth factor binding protein, and α2-macroglobulin. These results support the data mining approach for identifying gene and/or protein panels for assessing liver injury and may suggest bridging biomarkers for molecular mediators linked to histopathology.

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Section: Gene Signatures In Hepatotoxic Injurymentioning

confidence: 99%

Gene Expression Patterns Associated With Histopathology in Toxic Liver Fibrosis

et al. 2015

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“…Thus, HP is one of the factors involved in the progressive worsening of clinical conditions and histological changes observed in the cutaneous tissue of postbariatric patients. 13,14,52–54 Treatments capable of combating the inflammatory process on the skin of patients undergoing weight loss can reduce the deleterious effects of HP on collagenases and elastases, reducing foci of tissue fibrosis, 52–54 preserving skin elasticity, 22 and improving the clinical conditions of body contouring surgeries.…”

Section: Discussionmentioning

confidence: 99%

Skin Protein Profile after Major Weight Loss and Its Role in Body Contouring Surgery

Gallo

Maschio‐Signorini

Cabral

et al. 2019

Plastic and Reconstructive Surgery - Global Open

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Background:Chronic inflammation during morbid obesity significantly alters cutaneous tissue. Large weight loss achieved after bariatric surgery minimizes or halts damage caused by metabolic syndrome, but further deteriorates the clinical condition of skin. Postbariatric skin flaccidity produces major difficulties to plastic surgery. In this study, we analyzed differences in protein composition of the skin between patients with morbid obesity and those after large weight loss and established correlations between differentially expressed proteins and clinical characteristics of postbariatric skin tissue, to improve body contouring surgery techniques.Methods:Skin fragments were removed from the abdomen of 32 patients, who were allocated into 3 groups: morbidly obese, large weight loss without surgery, and postbariatric surgery. Samples were subjected to proteomic analysis, and the protein profiles of the groups were compared. Six differentially expressed proteins of clinical interest were validated by immunohistochemistry and statistical analysis.Results:Comparative analyses confirmed differences in protein profile of the skin between morbidly obese and large weight loss groups. A persistent increase in inflammatory markers such as haptoglobin was observed in all groups and decrease in the expression of collagen XIV, which regulates the physical properties of cutaneous tissue, was observed in the postbariatric group.Conclusions:High expression of haptoglobin associated with the decrease of Collagen XIV, vinculin, and periplakin in the groups after major weight losses, mainly postbariatric, confirm that the inflammatory lesion remains active in the skin and causes changes in its structural organization, with serious repercussions on its clinical characteristics and physical properties.

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“…42,43 However, recent evidence suggests that in some instances, the APR and/or its cytokines may enhance and/or accelerate pathologic processes. 16,[44][45][46][47] Indeed, patients with alcohol-induced hepatitis have clinical FIG. 5.…”

Section: Discussionmentioning

confidence: 99%

Rat hepatic stellate cells contribute to the acute-phase response with increased expression of α1(I) and α1(IV) collagens, tissue inhibitor of metalloproteinase-1, and matrix-metalloproteinase-2 messenger RNAs

Nieto¹,

Domı́nguez-Rosales²,

Fontana³

et al. 2001

Hepatology

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The acute-phase response (APR) represents a systemic reaction of the organism to multiple nonspecific inflammatory stimuli. In general, it is protective for the host, and hepatocytes are the main cells responding with alterations in the expression of a set of liver-specific proteins named the acute-phase proteins. We have previously shown that although a turpentine-induced APR is not fibrogenic per se, it enhances collagen deposition in rats treated with CCl(4) and up-regulates expression of hepatic alpha1(I) collagen and tissue inhibitor of metalloproteinases 1 (TIMP-1) messenger RNAs (mRNAs). In this report we extended our studies and showed that turpentine induced, in a time-dependent manner, expression of alpha1(I) and alpha1(IV) collagens, TIMP-1, and matrix-metalloproteinase 2 (MMP-2) mRNAs. We further showed that expression of these mRNAs occurs in hepatic stellate cells, but not in hepatocytes obtained 6 hours after the induction of an APR episode. These changes were accompanied by increased blood levels of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) without noticeable immediate changes in the expression of their respective mRNAs in the liver. In contrast to CCl(4)-induced liver damage, turpentine alone, whether administered as a single dose or as a weekly dose for 3 weeks did not up-regulate expression of transforming growth factor beta1 (TGF-beta1) mRNA and did not result in excess collagen deposition. Overall, these findings suggest that collagen deposition in the livers of rats with repeated APR episodes may be enhanced only when given together with a fibrogenic stimulus that activates hepatic stellate cells (HSCs) and/or up-regulates TGF-beta1 mRNA expression.

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Mechanisms by which acute phase proteins enhance development of liver fibrosis: Effects on collagenase and prolyl-4-hydroxylase activity in the rat liver

Cited by 17 publications

References 20 publications

Gene Expression Patterns Associated With Histopathology in Toxic Liver Fibrosis

Gene Expression Patterns Associated With Histopathology in Toxic Liver Fibrosis

Skin Protein Profile after Major Weight Loss and Its Role in Body Contouring Surgery

Rat hepatic stellate cells contribute to the acute-phase response with increased expression of α1(I) and α1(IV) collagens, tissue inhibitor of metalloproteinase-1, and matrix-metalloproteinase-2 messenger RNAs

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