論文 - 詳細
| RRC ID | 82832 |
|---|---|
| 著者 | Miyagawa-Hayashino A, Imura T, Takezawa T, Hirai M, Shibata S, Ogi H, Tsujikawa T, Konishi E. |
| タイトル | Activation of S1PR2 on macrophages and the hepatocyte S1PR2/RhoA/ROCK1/MLC2 pathway in vanishing bile duct syndrome. |
| ジャーナル | PLoS One |
| Abstract |
Immunologic bile duct destruction is a pathogenic condition associated with vanishing bile duct syndrome (VBDS) after liver transplantation and hematopoietic stem-cell transplantation. As the bile acid receptor sphingosine 1-phosphate receptor 2 (S1PR2) plays a critical role in recruitment of bone marrow-derived monocytes/macrophages to sites of cholestatic liver injury, S1PR2 expression was examined using cultured macrophages and patient tissues. Bile canaliculi destruction precedes intrahepatic ductopenia; therefore, we focused on hepatocyte S1PR2 and the downstream RhoA/Rho kinase 1 (ROCK1) signaling pathway and bile canaliculi alterations using three-dimensional hepatocyte culture models that form obvious bile canaliculus-like networks. Multiplex immunohistochemistry revealed increased numbers of S1PR2+CD45+CD68+FCN1+ inflammatory macrophages and S1PR2+CD45+CD68+MARCO+ Kupffer cells in liver tissues showing ductopenia due to graft-versus-host disease and rejection post-liver transplant compared with normal liver. Macrophage expression of proinflammatory cytokines, including MCP1, was reduced following S1PR2 inhibition. Taurocholic acid and S1P2 agonist induced hepatocyte S1PR2 and reduced RhoA/ROCK1 expression, resulting in bile canaliculi dilatation. S1PR2 inhibition reversed the effect on RhoA/ROCK1 expression, resulting in maintenance of bile canaliculi through myosin light chain 2 (MLC2) phosphorylation. Activation of S1PR2 on macrophages and S1PR2 on hepatocytes may disrupt bile canaliculi dynamics in VBDS under regulation by RhoA/ROCK1 through MLC2 phosphorylation. |
| 巻・号 | 20(1) |
| ページ | e0317568 |
| 公開日 | 2025-1-1 |
| DOI | 10.1371/journal.pone.0317568 |
| PII | PONE-D-24-29801 |
| PMID | 39854311 |
| PMC | PMC11760576 |
| MeSH | Adult Cardiac Myosins / metabolism Female Hepatocytes* / metabolism Hepatocytes* / pathology Humans Liver Transplantation / adverse effects Macrophages* / metabolism Male Middle Aged Myosin Light Chains* / metabolism Receptors, Lysosphingolipid / genetics Receptors, Lysosphingolipid / metabolism Signal Transduction* Sphingosine-1-Phosphate Receptors* / metabolism rho-Associated Kinases* / metabolism rhoA GTP-Binding Protein* / metabolism |
| IF | 2.74 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HepG2-NIAS(RCB4679) |