Journal article

Valproic Acid Initiates Transdifferentiation of the Human Ductal Adenocarcinoma Cell-line Panc-1 Into α-Like Cells


Authors listPetry, Sebastian Friedrich; Kandula, Naga Deepa; Guenther, Stefan; Helker, Christian; Schagdarsurengin, Undraga; Linn, Thomas

Publication year2022

Pages638-651

JournalExperimental and Clinical Endocrinology & Diabetes

Volume number130

Issue number10

ISSN0947-7349

eISSN1439-3646

DOI Linkhttps://doi.org/10.1055/a-1750-9190

PublisherThieme Publishing


Abstract
Non-mesenchymal pancreatic cells are a potential source for cell replacement. Their transdifferentiation can be achieved by triggering epigenetic remodeling through e. g. post-translational modification of histones. Valproic acid, a branched-chain saturated fatty acid with histone deacetylase inhibitor activity, was linked to the expression of key transcription factors of pancreatic lineage in epithelial cells and insulin transcription. However, the potential of valproic acid to cause cellular reprogramming is not fully understood. To shed further light on it we employed next-generation RNA sequencing, real-time PCR, and protein analyses by ELISA and western blot, to assess the impact of valproic acid on transcriptome and function of Panc-1-cells. Our results indicate that valproic acid has a significant impact on the cell cycle, cell adhesion, histone H3 acetylation, and metabolic pathways as well as the initiation of epithelial-mesenchymal transition through acetylation of histone H3 resulting in alpha-cell-like characteristics. We conclude that human epithelial pancreatic cells can be transdifferentiated into cells with endocrine properties through epigenetic regulation by valproic acid favoring an alpha-cell-like phenotype.



Citation Styles

Harvard Citation stylePetry, S., Kandula, N., Guenther, S., Helker, C., Schagdarsurengin, U. and Linn, T. (2022) Valproic Acid Initiates Transdifferentiation of the Human Ductal Adenocarcinoma Cell-line Panc-1 Into α-Like Cells, Experimental and Clinical Endocrinology & Diabetes, 130(10), pp. 638-651. https://doi.org/10.1055/a-1750-9190

APA Citation stylePetry, S., Kandula, N., Guenther, S., Helker, C., Schagdarsurengin, U., & Linn, T. (2022). Valproic Acid Initiates Transdifferentiation of the Human Ductal Adenocarcinoma Cell-line Panc-1 Into α-Like Cells. Experimental and Clinical Endocrinology & Diabetes. 130(10), 638-651. https://doi.org/10.1055/a-1750-9190



Keywords


BETA-CELLSDEVELOPING PANCREASEMBRYONIC PANCREASGLUCOSE-HOMEOSTASISHISTONE DEACETYLASEPANCREASSMALL-MOLECULE

Last updated on 2025-21-05 at 18:17