BACKGROUND/AIMS: Myofibroblasts play a central role in the pathogenesis of liver fibrosis. Myofibroblasts of bone marrow (BM) origin have recently been identified in fibrotic liver. However, little is known about the mechanism that controls their mobilization in vivo. Here we confirmed that BM mesenchymal stem cells (BMSCs) can migrate to the damaged liver and differentiate into myofibroblasts. We also investigated the mechanism underlying the homing of BMSCs after liver injury. METHODS: ICR mice were lethally irradiated and received BM transplants from enhanced green fluorescent protein transgenic mice. Carbon tetrachloride or bile duct ligation was used to induce liver fibrosis. The fibrotic liver tissue was examined by immunofluorescent staining to identify BM-derived myofibroblasts. RESULTS: BMSCs contributed significantly to myofibroblast population in fibrotic liver. Moreover, analysis in vivo and in vitro suggested that homing of BMSCs to the damaged liver was in response to sphingosine 1-phosphate (S1P) gradient between liver and BM. Furthermore, S1P receptor type 3 (S1P3) was required for migration of BMSCs triggered by S1P. CONCLUSIONS: S1P mediates liver fibrogenesis through homing of BMSCs via S1P3 receptor, which may represent a novel therapeutic target in liver fibrosis through inhibiting S1P formation and/or receptor activation.
BACKGROUND/AIMS: Myofibroblasts play a central role in the pathogenesis of liver fibrosis. Myofibroblasts of bone marrow (BM) origin have recently been identified in fibrotic liver. However, little is known about the mechanism that controls their mobilization in vivo. Here we confirmed that BM mesenchymal stem cells (BMSCs) can migrate to the damaged liver and differentiate into myofibroblasts. We also investigated the mechanism underlying the homing of BMSCs after liver injury. METHODS: ICR mice were lethally irradiated and received BM transplants from enhanced green fluorescent protein transgenic mice. Carbon tetrachloride or bile duct ligation was used to induce liver fibrosis. The fibrotic liver tissue was examined by immunofluorescent staining to identify BM-derived myofibroblasts. RESULTS: BMSCs contributed significantly to myofibroblast population in fibrotic liver. Moreover, analysis in vivo and in vitro suggested that homing of BMSCs to the damaged liver was in response to sphingosine 1-phosphate (S1P) gradient between liver and BM. Furthermore, S1P receptor type 3 (S1P3) was required for migration of BMSCs triggered by S1P. CONCLUSIONS:S1P mediates liver fibrogenesis through homing of BMSCs via S1P3 receptor, which may represent a novel therapeutic target in liver fibrosis through inhibiting S1P formation and/or receptor activation.
Authors: Changyong Li; Yuting Jin; Song Wei; Yishuang Sun; Longfeng Jiang; Qiang Zhu; Douglas G Farmer; Ronald W Busuttil; Jerzy W Kupiec-Weglinski; Bibo Ke Journal: Hepatology Date: 2019-06-21 Impact factor: 17.425
Authors: Elena Arriazu; Marina Ruiz de Galarreta; Francisco Javier Cubero; Marta Varela-Rey; María Pilar Pérez de Obanos; Tung Ming Leung; Aritz Lopategi; Aitor Benedicto; Ioana Abraham-Enachescu; Natalia Nieto Journal: Antioxid Redox Signal Date: 2014-01-08 Impact factor: 8.401
Authors: Gabriela Schneider; Ewa Bryndza; Ahmed Abdel-Latif; Janina Ratajczak; Magdalena Maj; Maciej Tarnowski; Yuri M Klyachkin; Peter Houghton; Andrew J Morris; Axel Vater; Sven Klussmann; Magdalena Kucia; Mariusz Z Ratajczak Journal: Mol Cancer Res Date: 2013-04-24 Impact factor: 5.852