Int J Med Sci 2020; 17(1):137-144. doi:10.7150/ijms.36337
Biological and Proteomic Characteristics of an Immortalized Human Pancreatic Stellate Cell Line
1. Department of Hepatic Biliary Pancreatic Medicine, First Hospital of Jilin University, Changchun, 130021, China
2. Research Institute at Nationwide Children's Hospital, Columbus, 43205, United States
*Sun L and Qu LM contributed equally to this article
Sun L, Qu L, Brigstock DR, Li H, Li Y, Gao R. Biological and Proteomic Characteristics of an Immortalized Human Pancreatic Stellate Cell Line. Int J Med Sci 2020; 17(1):137-144. doi:10.7150/ijms.36337. Available from http://www.medsci.org/v17p0137.htm
Human pancreatic stellate cells (PSCs) play a critical role in fibrogenesis during chronic pancreatitis (CP). However, primary PSCs have a short lifespan in vitro, which seriously affects their use in various applications. We have established a stable immortalized human PSC line (HP-1) by RSV promoter/enhancer-driven SV40 T antigen expression in primary activated human PSCs. HP-1 cells express cytoskeleton proteins including glial fibrillary acidic protein (GFAP), α-smooth muscle actin (α-SMA), vimentin and desmin, and are typical of PSCs, which are high transfeciability and viable in 0.5% serum. The cells express receptors such as TGFβR2, PDGFR, TGF-β pseudoreceptor Bambi and PPRPγ that are commonly found in PSCs. HP-1 cells are similar to activated human PSCs in that they have enhanced expression of α-SMA, CTGF, Col1 and TIMP-2 mRNAs or proteins, as well as decreased expression of MMP-1/2 mRNAs or proteins in response to TGF-β1 stimulation. Comparative proteomics revealed 4,537 shared proteins between HP-1 cells and PSCs and no single protein in HP-1 cells versus PSCs. Statistical analysis reveals no significantly difference between HP-1 cells and PSCs in their expression of proteins associated with matrix and matrix remodeling. The similarity between HP-1 cell and PSC is further shown by the finding that only 9 proteins are differentially up-regulated > ± 2-fold in HP-1 cells and 13 proteins are up-regulated > ± 2-fold in PSCs and none of these proteins include ECM proteins, cytokines, growth factors or matrix remodeling regulatory proteins. Therefore, HP-1 cells can be used as an effective tool for the study of PSC-mediated pancreatic fibrosis.
Keywords: human pancreatic stellate cell, immortalization, TGF-β1, pancreatic fibrosis, proteomics