| First Author | Masuzaki R | Year | 2021 |
| Journal | Am J Pathol | Volume | 191 |
| Issue | 2 | Pages | 309-319 |
| PubMed ID | 33159885 | Mgi Jnum | J:302357 |
| Mgi Id | MGI:6508204 | Doi | 10.1016/j.ajpath.2020.10.011 |
| Citation | Masuzaki R, et al. (2021) Integrin beta1 Establishes Liver Microstructure and Modulates Transforming Growth Factor beta during Liver Development and Regeneration. Am J Pathol 191(2):309-319 |
| abstractText | A unique and complex microstructure underlies the diverse functions of the liver. Breakdown of this organization, as occurs in fibrosis and cirrhosis, impairs liver function and leads to disease. The role of integrin beta1 was examined both in establishing liver microstructure and recreating it after injury. Embryonic deletion of integrin beta1 in the liver disrupts the normal development of hepatocyte polarity, specification of cell-cell junctions, and canalicular formation. This in turn leads to the expression of transforming growth factor beta (TGF-beta) and widespread fibrosis. Targeted deletion of integrin beta1 in adult hepatocytes prevents recreation of normal hepatocyte architecture after liver injury, with resultant fibrosis. In vitro, integrin beta1 is essential for canalicular formation and is needed to prevent stellate cell activation by modulating TGF-beta. Taken together, these findings identify integrin beta1 as a key determinant of liver architecture with a critical role as a regulator of TGF-beta secretion. These results suggest that disrupting the hepatocyte-extracellular matrix interaction is sufficient to drive fibrosis. |
