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 ( approximately 20 mean population division, MPD) and late-passage ( approximately 60 MPD) human skin fibroblasts to study the LDLr expression and MAPK at basal and after interleukin-1beta (IL-1beta) 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-1beta 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.
Donald W. Reynolds Department of Geriatrics, University of Arkansas for Medical Sciences and Medical Research, Central Arkansas Veterans Healthcare System, Little Rock, USA.
Chhanda
C
Bose
Chidambaram
C
Bhuvaneswaran
Kodetthoor B
KB
Udupa
D000375:Aging / Q000235:genetics* / Q000502:physiology; D000704:Analysis of Variance; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000032:analysis; D005347:Fibroblasts / Q000502:physiology*; D005786:Gene Expression Regulation; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D020935:MAP Kinase Signaling System; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D011336:Probability; D012313:RNA / Q000032:analysis; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D012867:Skin / Q000166:cytology
D018076:DNA, Complementary; D005819:Genetic Markers; D011973:Receptors, LDL; D012313:RNA; D020928:Mitogen-Activated Protein Kinases