title: Mechanism of interleukin-1β-induced proliferation in rat hepatic stellate cells from different levels of signal transduction.
abstract: Hepatic stellate cells (HSCs) are the major producers of collagen in the liver. Their conversion from resting cells to proliferative, contractile, and activated cells is a critical step leading to liver fibrosis that is characterized by the deposition of excessive extracellular matrix. Interleukin-1 (IL-1) may play a role in maintaining HSC in a proliferative state that is responsible for hepatic fibrogenesis. The aim of this study was to study the roles of the IL-1 type I receptor (IL-1R1), c-Jun N-terminal kinase (JNK), and activation protein-1 (AP-1) in IL-1β-mediated proliferation in rat HSCs. We showed that IL-1β can upregulate proliferation in rat HSCs; however, inhibition of the JNK pathway could inhibit HSCs proliferation. Furthermore, IL-1β activated IL-1R1 expression, the JNK signaling pathway, and AP-1 activity in a time-dependent manner in rat HSCs. These data demonstrate that IL-1β could promote the proliferation of rat HSCs and that the IL-1R1, JNK, and AP-1 pathways were involved in this process. In summary, IL-1β-induced proliferation is possibly mediated by the IL-1R1, JNK, and AP-1 pathways in rat HSCs. Therefore, drugs that block these pathways may inhibit the proliferation of HSCs and suppress liver fibrosis.
authors.affiliation: Department of Pediatrics, Third Hospital of Hebei Medical University.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Yaping
authors.forename: Wang
authors.initials: W
authors.lastname: Ying
authors.forename: Di
authors.initials: D
authors.lastname: Luqin
authors.forename: Tang
authors.initials: T
authors.lastname: Ning
authors.forename: Ai
authors.initials: A
authors.lastname: Xuemei
authors.forename: Yao
authors.initials: Y
authors.lastname: Xixian
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008103:Liver Cirrhosis / Q000188:drug therapy; D051381:Rats; D053573:Receptors, Interleukin-1 Type I / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D053583:Interleukin-1beta; D053573:Receptors, Interleukin-1 Type I; D018808:Transcription Factor AP-1; D048031:JNK Mitogen-Activated Protein Kinases
keywords: IL-1 type I receptor; Proliferation; activation protein-1; c-Jun N-terminal kinase; interleukin-1β