Role of c‐Jun N‐terminal kinase and p38/activation protein‐1 in interleukin‐1β‐mediated type I collagen synthesis in rat hepatic stellate cells
Abstract:Zhang Y, Yao X. Role of c‐Jun N‐terminal kinase and p38/activation protein‐1 in interleukin‐1β‐mediated type I collagen synthesis in rat hepatic stellate cells. APMIS 2011.
Interleukin‐1 (IL‐1) may play a role in maintaining hepatic stellate cell (HSC) in activated state that is responsible for hepatic fibrogenesis. However, the signal transduction pathway that is stimulated by IL‐1 in HSC remains to be fully elucidated. The aims of this study were to investigate the role of c‐Jun N‐terminal kinase (JNK) and p38/activation protein (AP‐1) in IL‐1β‐mediated type I collagen synthesis in rat HSCs. Here, we show that IL‐1β could activate JNK and p38 in a time‐dependent manner, and that inhibition of the JNK pathway could increase collagen synthesis; however, inhibition of the p38 pathway could inhibit collagen synthesis. Furthermore, IL‐1β activated AP‐1 in a time‐dependent manner in rat HSCs. These data demonstrate that L‐1β could promote the synthesis of type I collagen in rat HSCs, and the JNK and p38/AP‐1 pathways were involved in this process. In summary, IL‐1β‐induced collagen synthesis is possibly mediated by cytoplasmic JNK and p38/AP‐1 pathways. Therefore, drugs that block the p38/AP‐1 pathway may inhibit liver extracellular matrix synthesis and suppress liver fibrosis.
Document Type: Research Article
Affiliations: 1: Department of Pediatrics, The Third Hospital of Hebei Medical University, Shijiazhuang, China 2: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang, China
Publication date: February 1, 2012