**1. Introduction**

Liver fibrosis is characterized by pathological accumulation of extracellular matrix (ECM). ECM is a collection of molecules which are secreted by cells and distributed in all organs and tissues consisting of collagens, proteoglycans, glycoproteins and glycosaminoglycans [1]. Although some other cell types in the liver can also contribute to fibrosis, it is generally accepted that activated hepatic stellate cells (HSC) are the main source of excessive ECM. Integrins are a family of heterodimeric transmembrane receptors composed of an α and a β subunit, which are involved in cell-cell and cell-matrix interactions. Binding of integrins to ECM components mediates the recruitment and activation of signalling proteins such as focal adhesion kinase (FAK) and SRC kinase, which play a central role in the transduction of intracellular integrin signalling events. Furthermore, integrins have been reported to be involved in HSC activation and migration [2] and found to be upregulated during liver fibrosis [3].

UDCA-LPE is a synthetic bile acid-phospholipid conjugate, which has exhibited profound hepatoprotective and anti-fibrogenic functions in vitro and in vivo [4,5]. The conjugate contains an ursodeoxycholic acid (UDCA) moiety, which by itself also exhibits protective effects against hydrophobic bile-acid-induced hepatocellular apoptosis in cholestatic liver disease [6] and has been approved for the treatment of primary biliary cirrhosis [7].

Notably, our former studies revealed that protective functions of UDCA-LPE are critically dependent on the conjugation between the bile acid and the phospholipid whereas the individual compounds UDCA or LPE showed only little efficacy in different in vitro [4] and in vivo models [8]. These results imply that the conjugation due to its hydrophobicity is decisive in order to facilitate the interaction of UDCA-LPE with lipid membranes [9,10] rendering it a promising drug candidate for membrane lipid therapy [11].

Herein, we demonstrate the interaction of UDCA-LPE with integrins leading to integrin internalization via lipid rafts and subsequent inhibition of fibrogenic signalling. These events represent a novel mechanism of UDCA-LPE in support of its potent anti-fibrogenic effects previously observed in experimental mouse models of liver disease [5].
