Integrin β1 Establishes Liver Microstructure and Modulates Transforming Growth Factor β during Liver Development and Regeneration

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 beta 1 was examined both in establishing liver microstructure and recreating it after injury. Embryonic deletion of integrin beta 1 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 beta in adult hepatocytes prevents recreation of normal hepatocyte architecture after liver injury, with resultant fibrosis. In vitro, integrin rid is essential for canalicular formation and is needed to prevent stellate cell activation by modulating TGF-beta. Taken together, these findings identify integrin beta 1 as a key determinant of liver architecture with a critical role as a regulator of TGF-beta 1 secretion. These results suggest that disrupting the hepatocyte-extracellular matrix interaction is sufficient to drive fibrosis.

Automated summary

The liver's diverse functions rely on a unique and complex microstructure, which is disrupted in fibrosis and cirrhosis. Integrin beta 1 plays a crucial role in maintaining liver architecture and regulating TGF-beta 1 secretion. Disrupting the interaction between hepatocytes and their extracellular matrix is sufficient to drive fibrosis.