*2.1. UDCA-LPE Induces Translocation of Integrins*

The interaction with ECM leads to an autophosphorylation of FAK at Tyr397 with subsequent binding of FAK to SRC, which in turn activates SRC leading to phosphorylation of FAK at Tyr576/577 and Tyr925, which is known to be essential for its kinase activity [12]. After phosphorylation in response to integrin engagement, FAK and SRC trigger pro-fibrogenic signalling both in vivo and in vitro [13,14]. As non-kinase receptors, integrins activate FAK by a conformational change. Thus, the co-localization and interaction between integrins and FAK/SRC are considered to be essential for proper signalling. In the absence of UDCA-LPE, integrin β1 and SRC were found to be localized predominantly at cell-to-cell contacts of CL48 liver cells (Figure 1A). Upon addition of UDCA-LPE for 30 min, most of integrin β1 migrated away from plasma membrane while SRC localization was not affected (Figure 1A). After 2 h treatment, integrin β1 accumulated more pronouncedly at the nuclear envelope (Figure 1A). Despite of this integrin β1 translocation, the localization of active FAK (pFAK Tyr397) at the focal adhesions of CL48 cells was not affected by UDCA-LPE (Figure S1). UDCA-LPE-induced internalization of integrin β1 was also observed in HHStec cells (Figure S2A). The co-localization of integrin β1 and the endoplasmic reticulum (ER) marker calnexin in CL48 cells (Figure 1B) and HHStec cells (Figure S2B) upon UDCA-LPE treatment suggests the localization of endocytosed integrin β1 at the ER. Notably, treatment of CL48 cells with UDCA, LPE or UDCA + LPE had no effect on integrin β1 localization (Figure S3). Besides integrin β1, UDCA-LPE similarly induced the translocation of other integrins including integrin α2, α3, α5, αv, β4 and β5 (Figure S4). In the absence of UDCA-LPE, these integrins displayed some differences in terms of localization, that is, integrins α2, α3 and α5 localized at plasma membrane, integrin αv at the cytoplasm and integrin β5 at focal adhesions (Figure S5). However, the internalization of these integrins by UDCA-LPE was similar to that of integrin β1.

**Figure 1.** UDCA-LPE modulates the localization of integrin β1. Representative fluorescence microscopy images of CL48 cells after treatment with 90 μM UDCA-LPE for (**A**) 30 min or 2 h and (**B**) 1 h. Immunofluorescence showed the staining of (**A**) integrin β1 (green), SRC (red) and DAPI (blue) and (**B**) integrin β1 (green), calnexin (red) and DAPI (blue). DAPI was used for nuclear staining.
