2026-09-22T02:40:18Z https://www.ideals.illinois.edu/oai-pmh

oai:www.ideals.illinois.edu:2142/129315 2025-10-20 col_2142_5131 col_2142_5163 com_2142_5130 com_2142_5162 com_2142_234

application/pdf en text Submission original under an indefinite embargo labeled 'Open Access'. The submission was exported from vireo on 2025-10-19 without embargo terms The student, Ash Acharya, accepted the attached license on 2025-05-03 at 10:52. The student, Ash Acharya, submitted this Thesis for approval on 2025-05-03 at 11:00. This Thesis was approved for publication on 2025-05-05 at 15:47. DSpace SAF Submission Ingestion Package generated from Vireo submission #22197 on 2025-10-19 at 18:12:21 Angiogenic growth factors and notch signaling regulate liver sinusoidal endothelial cell phenotype in combination with matrix stiffness and ECM composition Acharya, Ash 2025-05-05 Underhill, Gregory H Notch Signaling VEGF FGF LSEC eng Liver sinusoidal endothelial cells (LSECs) are the first liver cells that allow metabolites to pass from the bloodstream to the hepatocytes, and as such, are important targets when detangling the effects of extracellular matrix proteins and mechanical cues on overall liver disease progression. Soluble growth factors such as VEGF and FGF have been shown to play complex roles in both inflammatory pathways (as part of liver disease), but also in liver regeneration via angiogenesis. In this study, a high throughput protein microarray based on polyacrylamide hydrogels of different stiffnesses was used to simultaneously look at the effects of time, stiffness, protein combination, soluble factors, and mechanical inhibition on LSEC phenotype using the markers VE-Cadherin (VECAD), CD-31, and LYVE-1. It was found that time increased expression of phenotypic markers, and enhanced the differences between the 1 and 25 kPa stiffness conditions for LYVE-1 expression. Stiffness was found to consistently increase VE-Cadherin localization, and decrease CD31 and LYVE-1 expression. Moreover, the ECM combination Collagen1/Hyaluronic Acid (C1HA) consistently had the highest LYVE-1 expression across many different conditions. Notably, VEGF caused an increase in LYVE-1 expression on the soft 1kPa stiffness condition, but caused a decrease in the 25kPa condition. FGF followed a similar, if nonsignificant trend. DAPT, a Notch inhibitor drug, also unilaterally caused a decrease in LYVE-1 expression across the board, and in combination with VEGF, unilaterally increased VECAD localization and decreased LYVE-1 expression in relation to every other condition. This data could partially suggest that VEGF’s positive effects on LYVE-1 expression, and LSEC phenotype could be in part modulated by Notch, and in inhibiting Notch, VEGF has negative effects on LSEC phenotype. 2025-05 Thesis https://hdl.handle.net/2142/129315 Copyright 2025 Ash Acharya Bioengineering Bioengineering University of Illinois Urbana-Champaign M.S. Thesis