Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0239946 (liver fibrosis)
 8,268 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Undulin and fibronectin (FN) are large extracellular matrix (ECM) glycoproteins possibly involved in cell-matrix interactions. In this study we analyzed the effect of acetaldehyde and transforming growth factor-beta 1 (TGF-beta 1) on undulin and FN synthesis in cultured fat-storing cells (FSC) isolated from wedge sections of normal human livers. Cultured human FSC expressed two mRNA transcripts (6.5 and 8.5 kb) specific for undulin. Acetaldehyde inhibited both undulin mRNA and protein expression, whereas it had an opposite (stimulatory) effect on FN synthesis. TGF-beta 1 induced a dose-dependent increase of both undulin and FN synthesis in FSC cultures. Furthermore, TGF-beta 1 antagonized the inhibitory effect of acetaldehyde on undulin production and potentiated the stimulatory effect of acetaldehyde on FN synthesis. Since undulin is involved in the supramolecular organization of fibrillar collagens and in their enzymatic degradation, its acetaldehyde-induced inhibition may contribute to ECM rearrangement in the early stages of alcoholic liver fibrosis.
 ...
PMID:Regulation of undulin synthesis and gene expression in human fat-storing cells by acetaldehyde and transforming growth factor-beta 1: comparison with fibronectin. 813 74

Activation and transformation of lipocytes (Ito cells, stellate cells) into alpha-actin-positive myofibroblast-like cells is an essential step in the initiation of liver fibrosis. Transforming growth factor-beta (TGF-beta) is considered an important mediator of this process. In order to determine mechanisms of fibrotic deposition in a hepatic transplant setting, we analyzed 10 chronically rejected human liver allografts for the expression of extracellular matrix (ECM) molecules, myofibroblast-like cells (alpha-actin), macrophages, and TGF-beta1 and -beta3. Using single- and double-immunohistochemical staining techniques, all specimens investigated showed increased deposition of the ECM proteins fibronectin, tenascin, undulin, and collagen VI with a characteristic densification especially in pericentral areas. Likewise, strong accumulation of alpha-actin-positive cells and TGF-beta1-expressing macrophages was observed in the same fields, supporting the concept of lipocyte activation/transformation and subsequent ECM production fostered by macrophage-derived TGF-beta1. In contrast, TGF-beta3 was found to be mainly expressed by a markedly increased number of lipocytes. Interestingly, distribution of TGF-beta3 corresponded to that of tenascin, an ECM molecule known to be involved in early matrix organization, suggesting that TGF-beta3 may likewise act mainly in early stages of fibrogenesis. Furthermore, TGF-beta3 restriction to high numbers of a single cell type (i.e., lipocytes) implied a possible role in cell proliferation through autocrine loops. In conclusion, fibrosis in chronic rejection seems to follow similar mechanisms as in non-transplanted livers but additionally suggests differential temporal and functional roles for the TGF-beta isoforms 1 and 3 in the course of a multistep process leading to lipocyte transformation and ECM production.
 ...
PMID:Fibrosis in chronic rejection of human liver allografts: expression patterns of transforming growth factor-TGFbeta1 and TGF-beta3. 899 Mar 62

A number of circulating breakdown products of collagen or other components of extracellular matrix, matrix degrading metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) have been proposed as markers of hepatic fibrosis. However, the published results lack consistency. Since many of the patients with fibrosis studied were alcoholics, the question was raised whether recent alcohol consumption may affect the results obtained. Using sandwich-type assays of radioimmunoassay technology with corresponding antibodies, we studied eight markers of liver fibrosis: laminin, tenascin, undulin, TIMP-1, collagen VI, procollagen type III (PIIINP), hyaluronic acid (HA) and MMP-2. A group of 10 alcoholics was studied after significant alcohol consumption and following 2 weeks of abstinence, verified with repeated breath alcohol measurement. Laminin was significantly reduced at 1 week (22%) and at 2 weeks (30%). Similarly, tenascin and undulin were also significantly decreased. By contrast, TIMP-1, collagen VI, PIIINP, HA and MMP-2 did not significantly change. The mode of action of alcohol on these tests is unknown. These differences must be considered when using those measurements to assess liver fibrosis.
 ...
PMID:Effects of alcohol consumption on eight circulating markers of liver fibrosis. 1200 13

Liver fibrosis and cirrhosis are common sequelae to diverse liver injuries in the tropics or Nigeria. The development of hepatic fibrosis or cirrhosis is due to increased synthesis, deposition, and possibly reduced degradation of hepatic extracellular matrix components, especially collagens, such as interstitial type I and III, basement membrane type IV, microfibrillar type VI, and pericellular type V, non-collagenous proteins, such as laminin, fibronectin, undulin, etc., and various types of proteoglycans, such as hyaluronan, etc. In Nigeria, the common approach for diagnosing or assessing the activity of connective tissue in this organ is the histological examination of a biopsy, if one is performed by a specialist physician. The liver biopsy provides a static picture of the changes that have already taken place in the liver. Another possible method is (where the facilities are available) a quantitative assessment of the liver biopsy by biochemical determination of total collagen via hydroxyproline. Biopsy is an invasive method and cannot be repeated often enough in the bid to ensuring an intensive follow-up of the changes taking place during the course of antifibrotic treatment or therapy. Thus, serum or other biological fluid assays for connective tissue proteins, such as the aminoterminal propeptide of type III Procollagen PIIINP, or the dimeric carboxyterminal domain of type IV collagen known as NCl or PIVCP, laminin, and others are essentially non-invasive and can be carried out repeatedly. In addition, the measurement of certain enzymes of connective tissue proteins in serum may the reflect activity of liver fibrogenesis. They offer the potential for diagnosis and therapeutic control. However, it is very important to note that circulating biochemical markers of fibrogenesis, fibrolysis or both may not reflect hepatic fibrosis or cirrhosis, since they are not liver-specific. Thus, the best diagnostic approach would be the identification and measurement in serum of the driving force of fibrogenic process.
 ...
PMID:Biochemical markers, extracellular components in liver fibrosis and cirrhosis. 1768 72