Fig. 6
From: Targeting integrin pathways: mechanisms and advances in therapy
Roles of integrins in fibrosis processes in NASH, PH, and ADPKD. The lower part of the circle shows the role of integrins in liver fibrosis in NASH. In hepatic cells (HCs), activated integrin α9β1 is endocytosed by hepatocytes and secreted in the form of extracellular vesicles (EVs), which are further captured by MoMFs. Captured integrin α9β1 mediates MoMF adhesion to liver sinusoidal endothelial cells (LSECs) by binding to VCAM-1, which accelerates liver fibrosis. In HSCs, integrin α8β1 promotes liver fibrosis by activating TGF-β. The binding of integrin αvβ3 with OPN could promote laminin and α-SMA expression, which causes ECM accumulation and fibrosis progression. Integrin αvβ5 also binds with OPN and enhances liver fibrosis, but the underlying mechanism still needs to be clarified. In CD4 + T cells, the adhesion between integrin α4β7 and HC expressing MAdCAM-1 recruits CD4 + T cells to the liver, which induces liver inflammation and fibrosis. The left part of the circle shows the role of integrins in intimal fibrosis in PH. In the progression of PH, integrin α1, α8, αv, β1, and β3 are upregulated, and α5 is downregulated in PASMCs. Integrin α1 increases and α5 decreases the concentration of Ca2 + , promoting intimal fibrosis. The binding between integrin αvβ3 and OPN activates FAK signal transduction, which might be involved in the processes of vascular remodeling. The right part of the circle shows the role of integrins in renal fibrosis in ADPKD. Integrin αvβ3 expressed in renal tubular epithelial cells binds with periostin, activating TGF-β and promoting renal fibrosis. Binding between integrin αvβ3 and OPN is also involved in the renal fibrosis process, but the underlying mechanism is unclear. Renal tubular epithelial cells expressing integrin β1 enhance the expression of collagen, fibronectin, and α-SMA, which promote renal fibrosis
