Different cellular properties and loss of nuclear signalling of porcine epidermal growth factor receptor with aging

Abstract Epidermal growth factor (EGF) has important physiological functions that are mediated by the epidermal growth factor receptor (EGFR); however, to date, the changes in cellular behaviours and signalling properties of EGF/EGFR with aging remain unclear in the pig tissue models. Hence, the present study used porcine hepatocytes as a model to explore this issue. The study revealed the following results: 1) EGF could activate the intra-cellular signalling pathways in a time- and dose-dependent manner both in the young- and aged-pig hepatocytes, EGF induced tyrosine phosphorylation of EGFR, signal transducers and activators of transcription 3 (STAT3), protein kinase B (AKT) and extra-cellular signal-regulated kinase 1/2 (ERK1/2). Nevertheless, the EGF’s signalling ability in the aged-pig hepatocytes was significantly reduced compared with that of the young-pig hepatocytes; 2) although EGF/EGFR can still be internalised into cells in a time-dependent manner with aging, the endocytic pathway differs between the young- and aged-pig hepatocytes. Furthermore, the results of the present study indicated that caveolin may play a pivotal role in the endocytosis of EGF/EGFR in the aged-pig hepatocytes, which is different from that of EGF/EGFR’s endocytosis in young-pig hepatocytes; 3) It is well-known that EGFR carried out its biological effects via two signalling pathways, cytoplasmic pathway (traditional) and nuclear pathway; however, we found that the nuclear localisation of EGFR was significantly reduced in the aged-pig hepatocytes, which indicated that EGFR may lose its nuclear pathway with aging. Collectively, the present study lays the foundation for further study regarding the biological functional changes occurring in EGF/EGFR with aging.