| First Author | Fortier M | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 14614 |
| PubMed ID | 31601995 | Mgi Jnum | J:285294 |
| Mgi Id | MGI:6389506 | Doi | 10.1038/s41598-019-51175-z |
| Citation | Fortier M, et al. (2019) Hepatospecific ablation of p38alpha MAPK governs liver regeneration through modulation of inflammatory response to CCl4-induced acute injury. Sci Rep 9(1):14614 |
| abstractText | Mammalian p38alpha MAPK (Mitogen-Activated Protein Kinase) transduces a variety of extracellular signals that regulate cellular processes, such as inflammation, differentiation, proliferation or apoptosis. In the liver, depending of the physiopathological context, p38alpha acts as a negative regulator of hepatocyte proliferation as well as a promotor of inflammatory processes. However, its function during an acute injury, in adult liver, remains uncharacterized. In this study, using mice that are deficient in p38alpha specifically in mature hepatocytes, we unexpectedly found that lack of p38alpha protected against acute injury induced by CCl4 compound. We demonstrated that the hepatoprotective effect alleviated ROS accumulation and shaped the inflammatory response to promote efficient tissue repair. Mechanistically, we provided strong evidence that Ccl2/Ccl5 chemokines were crucial for a proper hepatoprotective response observed secondary to p38alpha ablation. Indeed, antibody blockade of Ccl2/Ccl5 was sufficient to abrogate hepatoprotection through a concomitant decrease of both inflammatory cells recruitment and antioxidative response that result ultimately in higher liver damages. Our findings suggest that targeting p38alpha expression and consequently orientating immune response may represent an attractive approach to favor tissue recovery after acute liver injury. |
