New research has shown that αv integrins are a core component of a molecular pathway that underlies the development of fibrosis in multiple organs, including the liver. “Therapeutically targeting all αv integrins effectively treated fibrosis in multiple organs,” explains author Neil Henderson, offering hope for new targeted antifibrotic therapies.

Henderson and co-workers developed a model system, using Pdgfrb-Cre mice, to study the effects of αv integrins in the context of fibrosis. Depletion of αv integrins in hepatic stellate cells (a major source of myofibroblasts in the liver) protected mice from developing liver fibrosis upon treatment with carbon tetrachloride (CCl4). Importantly, individual depletion of multiple binding partners for the αv subunit (β3, β5 and β6 integrins, or conditional depletion of β8 integrin on myofibroblasts) failed to protect mice from CCl4-induced liver fibrosis—a finding that Henderson believes is because “inhibition of multiple αv integrins is probably required to effectively treat liver fibrosis”.

Crucially, use of a small-molecule inhibitor of αv integrins (CWHM 12) substantially reduced the development of fibrosis in the liver and in the lung. Moreover, CWHM 12 reduced liver fibrosis even after the disease was well established.

“Comprehensive testing of CWHM 12 will be required before consideration of clinical trials,” notes Henderson, who plans to investigate a variety of different genes in myofibroblasts in the quest for further novel antifibrotic targets.