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Altered Mitogen-Activated Protein Kinase Signal Transduction in Human Skin Fibroblasts During In Vitro Aging: Differential Expression of Low-Density Lipoprotein Receptor

¹ Donald W. Reynolds Department of Geriatrics
² Department of Biochemistry and Molecular Biology
³ Department of Physiology and Biophysics, University of Arkansas for Medical Sciences and Medical Research, Central Arkansas Veterans Healthcare System, Little Rock.

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-1ß (IL-1ß) 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-1ß 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.