Cadherin-11 contributes to liver fibrosis induced by carbon tetrachloride

• Published in: PloS one Vol. 14; no. 7; p. e0218971
• Main Authors: Pedroza, Mesias, To, Sarah, Smith, Jennifer, Agarwal, Sandeep K
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 03.07.2019; Public Library of Science (PLoS)
• Subjects: Actin; Animals; Arthritis; Biology and Life Sciences; Bone morphogenetic proteins; Cadherins; Cadherins - genetics; Carbon; Carbon tetrachloride; Carbon Tetrachloride - toxicity; Care and treatment; Cell adhesion & migration; Cells, Cultured; Cirrhosis; Collagen; Collagen - genetics; Cytokines; Deposition; Development and progression; Experiments; Extracellular matrix; Extracellular Matrix - drug effects; Extracellular Matrix - genetics; Fibroblasts; Fibrosis; Gene expression; Growth factors; Halides; Health aspects; Hepatic Stellate Cells - metabolism; Hepatic Stellate Cells - pathology; Hepatocytes; Hepatocytes - drug effects; Hepatocytes - metabolism; Hepatology; Histology; Humans; Immunoglobulins; Immunology; Interleukin 6; Liver; Liver - drug effects; Liver - metabolism; Liver - pathology; Liver cirrhosis; Liver Cirrhosis - chemically induced; Liver Cirrhosis - genetics; Liver Cirrhosis - pathology; Liver diseases; Lung diseases; Macrophages; Medical research; Medicine; Medicine and Health Sciences; Messenger RNA; Mice; Mice, Knockout; mRNA; Muscle proteins; Muscles; Pulmonary fibrosis; Research and Analysis Methods; Respiratory tract diseases; Rheumatology; RNA; Skin; Smooth muscle; Stellate cells; Therapeutic applications; Transforming Growth Factor beta - genetics; Transforming growth factors; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0218971

Liver fibrosis is characterized by the excessive deposition of extracellular matrix (ECM) leading to impaired function and cirrhosis. Previous reports support a role for cadherin-11 (CDH11) in regulating the development of dermal and pulmonary fibrosis. In the current report, the extent to which CDH11 modulates the development of liver fibrosis induced by carbon tetrachloride (CCL4) was assessed. Wild type (WT) and CDH11 deficient (CDH11-/-) mice were treated with CCl4 or vehicle control for 8 weeks to induce liver fibrosis. Liver fibrosis was assessed by histology, collagen content, and RTPCR of fibrotic mediators. Livers from WT mice treated with CCl4 had increased levels of CDH11 which localized to injured hepatocytes, hepatic stellate cells, and macrophages. Interestingly, CDH11-/- mice had decreased histological evidence of liver fibrosis, collagen deposition, α-smooth muscle actin (α-SMA) accumulation, and mRNA levels of fibrotic mediators such as Col1-α1, Snail, TGF-β and IL-6. These data demonstrate that CDH11 is increased during liver fibrosis, is an important regulator of liver fibrosis induced by CCL4 and suggest that CDH11 may be a potential therapeutic target for liver fibrosis.