title: Low concentrations of bilirubin inhibit activation of hepatic stellate cells in vitro.
abstract: Hepatic stellate cell (HSC) activation serves a key role in liver fibrosis, and is associated with chronic liver diseases. Bilirubin, a product of heme degradation, has been demonstrated to have antioxidant properties. The present study investigated the effects of physiological concentrations of bilirubin on rat HSC activation. Rat HSCs were isolated and cultured for several generations to induce activation. The activated HSCs were subsequently treated with 0, 1, 10 or 20 mg/l bilirubin and assayed for parameters of cell activation. As the bilirubin concentration increased, HSCs demonstrated reduced production of reactive oxygen species, reduced protein expression levels of α‑smooth muscle actin, a decreased mRNA expression ratio of tissue inhibitor of matrix metalloproteinase‑1/matrix metalloproteinase‑2, decreased proliferation and increased apoptosis. In conclusion, elevated bilirubin levels, within its physiological concentration range, appeared to inhibit HSC activation. These findings suggested a potential role for bilirubin in the treatment of fibrosis that requires further investigation.
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Yinhe
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Qiyu
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Yefan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Fuxiang
authors.initials: F
authors.lastname: Yu
mesh_terms: D000199:Actins; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001663:Bilirubin / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D055166:Hepatic Stellate Cells / Q000166:cytology* / Q000187:drug effects; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D001663:Bilirubin; D020778:Matrix Metalloproteinase 2; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D019715:Tissue Inhibitor of Metalloproteinase-1; C498862:Acta2 protein, rat