Pancreatic stellate cell models for transcriptional studies of desmoplasia-associated genes.

Publication Type:

Journal Article

Source:

Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.], Volume 10, Issue 4, p.505-16 (2010)

Keywords:

Animalsdigestive disease, digestive deseases Cell Culture Techniquesdigestive disease, digestive deseases Cell Line, Transformeddigestive disease, digestive deseases Cell Survivaldigestive disease, digestive deseases Fibrosisdigestive disease, digestive deseases Gene Expression Regulation, Neoplasticdigestive disease, digestive deseases Hepatic Stellate Cellsdigestive disease, digestive deseases Humansdigestive disease, digestive deseases Micedigestive disease, digestive deseases Mice, Inbred C57BLdigestive disease, digestive deseases Mice, Nudedigestive disease, digestive deseases Pancreatic Neoplasmsdigestive disease, digestive deseases Pancreatic Stellate Cellsdigestive disease, digestive deseases Ratsdigestive disease, digestive deseases Rats, Sprague-Dawleydigestive disease, digestive deseases Transcription, Geneticdigestive disease, digestive deseases Transfection

Abstract:

BACKGROUND: Pancreatic stellate cells are emerging as key players in pathophysiopathological processes underlying the development of pancreatic disease, including pancreatitis and cancer. The cells are scarce in the pancreas making their isolation time and resource use consuming.

METHODS: Therefore, with the ultimate goal of facilitating mechanistic studies, here we report the isolation, characterization, and immortalization of stellate cell lines from rat and mouse origin.

RESULTS: These cell lines display morphological and molecular markers as well as non-tumorigenic characteristics similar to the frequently used hepatic counterparts. In addition, we have tested their robustness as a model for transcriptional regulatory studies. We find that these cells respond well to TGFβ signaling by triggering a distinct cascade of gene expression, some genes overlap with the TGFβ response of LX2 cells. These cells express several key chromatin proteins and epigenetic regulators involved in the regulation of gene expression, including co-repressors such as Sin3A (short-term repression), HP1 (long-term repression), as well as CBP/p300 (activation). Furthermore, these cells are well suited for Gal4-based transcriptional activation and repression assays.

CONCLUSIONS: The cell model reported here may therefore help fuel investigations in the field of signaling, transcription, and perhaps other studies on similarly exciting cellular processes. and IAP.