Elastin in the Liver

Abstract

A characteristic feature of liver cirrhosis is the accumulation of large amounts of connective tissue with the prevailing content of type I collagen. Elastin is a minor connective tissue component in normal liver but it is actively synthesized by hepatic stellate cells and portal fibroblasts in diseased liver. The accumulation of elastic fibers in later stages of liver fibrosis may contribute to the decreasing reversibility of the disease with advancing time. Elastin is formed by polymerization of tropoelastin monomers. It is an amorphous protein highly resistant to the action of proteases that forms the core of elastic fibers. Microfibrils surrounding the core are composed of fibrillins that bind a number of proteins involved in fiber formation. They include microfibril-associated glycoproteins (MAGPs), microfibrillar-associated proteins (MFAPs) and fibulins. Lysyl oxidase (LOX) and lysyl oxidase-like proteins (LOXLs) are responsible for tropoelastin cross-linking and polymerization. TGF-β complexes attached to microfibrils release this cytokine and influence the behavior of the cells in the neighborhood. The role of TGF-β as the main profibrotic cytokine in the liver is well-known and the release of the cytokines of TGF-β superfamily from their storage in elastic fibers may affect the course of fibrosis. Elastic fibers are often studied in the tissues where they provide elasticity and resilience but their role is no longer viewed as purely mechanical. Tropoelastin, elastin polymer and elastin peptides resulting from partial elastin degradation influence fibroblastic and inflammatory cells as well as angiogenesis. A similar role may be performed by elastin in the liver. This article reviews the results of the research of liver elastic fibers on the background of the present knowledge of elastin biochemistry and physiology. The regulation of liver elastin synthesis and degradation may be important for the outcome of liver fibrosis.

Quantitative assessment of liver fibrosis reveals a nonlinear association with fibrosis stage in nonalcoholic fatty liver disease

“…However, the potential role of elastin fiber deposition in the irreversibility of chronic liver diseases remains poorly understood. Our quantitative fibrosis data suggest that elastin fiber is a minor fibrous component in the early stages of fibrosis but may accumulate in areas of thick bridging fibrosis, fibrous septa, or venous walls at the cirrhosis stage of NAFLD, a finding that is consistent with studies on various chronic liver diseases . Our previous study attested to the positive association of higher elastin area ratios (≥3.6%) with the risk of hepatocellular carcinoma in patients with hepatitis C virus infection .…”

“…Our quantitative fibrosis data suggest that elastin fiber is a minor fibrous component in the early stages of fibrosis but may accumulate in areas of thick bridging fibrosis, fibrous septa, or venous walls at the cirrhosis stage of NAFLD, a finding that is consistent with studies on various chronic liver diseases. (46,47) Our previous study attested to the positive association of higher elastin area ratios (3.6%) with the risk of hepatocellular carcinoma in patients with hepatitis C virus infection. (36) In the current NAFLD cohort, 22 (24%) of 92 patients with advanced NAFLD (4 of 41 with stage 3; 18 of 51 with stage 4) had elastin area ratios greater than or equal to 3.6%, whereas none of 162 patients with early fibrosis with stages 1/2 harbored this amount of elastin in liver biopsy specimens.…”

“…Evidence suggests that fibrosis can progress but it may also regress during the disease course of NAFLD. (45) Considering the biochemically stable nature of elastin compared with collagen, (46) elastin accumulation in the liver may contribute to the irreversibility of the disease. However, the potential role of elastin fiber deposition in the irreversibility of chronic liver diseases remains poorly understood.…”

Is the Total Amount as Important as Localization and Type of Collagen in Liver Fibrosis Attributable to Steatohepatitis?

“…(36) The bridging pattern of fibrosis ultimately leads to encapsulation of liver lobules (regenerative nodules) that are further damaged because of vascular undersupply. (37) Hence, the reparative potential and activities of the tissue are fundamentally altered. When regenerative nodules are present, the histological criteria for liver cirrhosis are fulfilled, corresponding to fibrosis stage F4.…”

Advanced Biomaterials and Processing Methods for Liver Regeneration: State‐of‐the‐Art and Future Trends

“…The silk‐based platforms were already systematically reviewed by Kundu et al Regarding elastin, it is one of the most stable proteins of the ECM, being present in large amounts in those elastic organs such as arteries and lungs. Kanta et al suggested that the dysregulation of elastin synthesis and metabolism may be an essential cause for liver fibrosis. Laminin is a structural protein in the ECM of skeletal muscle fibers that plays an important role in tissue development, maintenance, and function regulation …”