Preprint Article Version 1 This version is not peer-reviewed

Collagen I Exacerbates Palmitate-Induced Cell Death in HepG2 Cells via Integrin-Mediated Death

Version 1 : Received: 12 August 2024 / Approved: 13 August 2024 / Online: 14 August 2024 (07:15:43 CEST)

How to cite: Maseko, T. E.; Peterová, E.; Elkalaf, M.; Koutová, D.; Melek, J.; Staňková, P.; Špalková, V.; Matar, R.; Lotková, H.; Červinková, Z.; Kučera, O. Collagen I Exacerbates Palmitate-Induced Cell Death in HepG2 Cells via Integrin-Mediated Death. Preprints 2024, 2024080953. https://doi.org/10.20944/preprints202408.0953.v1 Maseko, T. E.; Peterová, E.; Elkalaf, M.; Koutová, D.; Melek, J.; Staňková, P.; Špalková, V.; Matar, R.; Lotková, H.; Červinková, Z.; Kučera, O. Collagen I Exacerbates Palmitate-Induced Cell Death in HepG2 Cells via Integrin-Mediated Death. Preprints 2024, 2024080953. https://doi.org/10.20944/preprints202408.0953.v1

Abstract

Various strategies have been employed to improve the reliability of 2D, 3D, and co-culture in vitro models of nonalcoholic fatty liver disease, including using extracellular matrix proteins, such as collagen I, to promote cell adhesion. While studies have demonstrated the significant benefits of culturing cells on collagen I, its effects on HepG2 and HepaRG cell lines after exposure to palmitate (PA) have not been investigated. Therefore, this study aimed to assess the effects of PA-induced lipotoxicity in HepG2 and HepaRG cultured in the absence or presence of collagen I. HepG2 and HepaRG cultured in the absence or presence of collagen I were exposed to PA, followed by analyses that assessed cell proliferation, viability, adhesion, cell death, mitochondrial respiration, reactive oxygen species production, gene and protein expressions, and triacylglycerol accumulation. Culturing HepG2 on collagen I was associated with increased cell proliferation, adhesion, expression of integrin receptors, and improved cellular spreading compared to culturing them in the absence of collagen I. PA-induced lipotoxicity was greater in collagen I-cultured HepG2 than those cultured in the absence of collagen I. In summary, the present study demonstrated for the first time that collagen I-cultured HepG2 exhibited exacerbated cell death following exposure to PA through integrin-mediated death. The findings from this study may serve as a caution to those using 2D models or 3D scaffold-based models of HepG2 in the presence of collagen I.

Keywords

in vitro NAFLD models; collagen I; palmitate; lipotoxicity; α2β1 receptors; integrin-mediated death; HepG2 cells

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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