Altered mitogen-activated protein kinase signal transduction in human skin fibroblasts during in vitro aging: differential expression of low-density lipoprotein receptor

The purpose of the study was to investigate the correlation of low-density lipoprotein receptor (LDLr) and mitogen-activated protein kinases (MAPK) in fibroblasts after serial passage in vitro. We used early-passage (~20 mean population division, MPD) and late-passage (~60 MPD) human skin fibroblasts to study the LDLr expression and MAPK at basal and after interleukin-1[beta] (IL-1[beta]) stimulation. We found a reduced LDLr expression in late-passage fibroblasts in comparison with early-passage fibroblasts, and late-passage fibroblasts showed a delayed induction of MAPK after IL-1[beta] stimulation, confirmed by the delay in translocation of MAPK from cytoplasmic to nuclear fraction. Using two specific inhibitors of MAPK, we could show a reduced LDLr expression in early-passage fibroblasts, indicating a direct relationship between MAPK signaling and LDLr expression. We conclude that one of the reasons for reduced LDLr gene expression in late passage fibroblast is related to MAPK signaling.