| Journal: | Annals of hepatology |
| Database: | PERIÓDICA |
| System number: | 000407206 |
| ISSN: | 1665-2681 |
| Authors: | Beier, Juliane I1 Guo, Luping1 Joshi-Barve, Swati1 Ritzenthaler, Jeffrey D1 Roman, Jesse1 Arteel, Gavin E1 |
| Institutions: | 1University of Louisville, Health Sciences Center, Louisville, Kentucky. Estados Unidos de América |
| Year: | 2016 |
| Season: | Sep-Oct |
| Volumen: | 15 |
| Number: | 5 |
| Pages: | 762-772 |
| Country: | México |
| Language: | Inglés |
| Document type: | Artículo |
| Approach: | Analítico, descriptivo |
| English abstract | The Background. regenerative capacity of the liver is critical for proper responses to injury. Fibrin extracellular matrix (ECM) deposition is a common response to insult and contributes to inflammatory liver injury. However, the role of this matrix in hepatic regeneration has not been determined. Objective. Objective. The Objective. purpose of this study was first to determine the role of fibrin ECM in hepatic regeneration followed by the role of the fibrin-binding αv β3 integrin in mediating this effect. Material and methods. Material and methods. C57Bl/6J Material and methods. (WT) or PAI-1 knockout (KO) mice underwent 70% partial hepatectomy (PHx); plasma and histologic indices of regeneration were determined, as well as expression of key genes involved in hepatic regeneration. Results. Results. PHx promoted transient fibrin deposition Results. by activating coagulation and concomitantly decreasing fibrinolysis. Inhibiting fibrin deposition, either by blocking thrombin (hirudin) in WT mice or by knocking out PAI-1, was associated with a decrease in hepatocyte proliferation after PHx. This strongly suggested a role for fibrin ECM in liver regeneration. To investigate if αv β3 integrin mediates this action, we tested the effects of the anti-αv β3 cyclic peptide RGDfV in animals after PHx. As was observed with inhibition of fibrin deposition, competitive inhibition of αv β3 integrin delayed regeneration after PHx, while not affecting fibrin deposition. These effects of RGDfV correlated with impaired angiogenesis and STAT3 signaling, as well as transient endothelial dysfunction. In conclusion, these data suggest that αv β3 integrin plays an important role in coordinating hepatocyte division during liver regeneration after PHx via crosstalk with fibrin ECM |
| Disciplines: | Medicina |
| Keyword: | Gastroenterología, Medicina experimental, Biología celular, Regeneración hepática, Hepatocitos, Matriz extracelular, División celular, Fibrina, Integrinas |
| Keyword: | Medicine, Experimental medicine, Gastroenterology, Cell biology, Liver regeneration, Hepatocytes, Extracellular matrix, Cell division, Fibrin, Integrins |
| Full text: | Texto completo (Ver PDF) |
