Related Experiment Videos
Age related induction of platelet-derived growth factor A-chain mRNA in normal human fibroblasts
1Department of Pathology, University Hospital, Uppsala, Sweden.
Abstract:
We have previously found that stimulation of normal neonatal fibroblasts with PDGF or EGF leads to a transient induction of PDGF A-chain mRNA and the synthesis of PDGF-AA proteins. This finding may imply the existence of an autocrine feedback mechanism to amplify the mitogenic signal under certain conditions. We have now studied the PDGF-BB mediated PDGF A-chain induction in a set of fibroblasts from young and old donors to clarify if the levels of induction are correlated to the donor age and the replicative capacity of the cells. The PDGF A-chain induction was found to be reduced in cells from old donors compared with cells from embryonic and neonatal donors. The different cell strains were also characterized further with respect to PDGF receptor expression and PDGF binding properties. PDGF beta-receptors were found to be enhanced in old donor cell strains, whereas the PDGF alpha-receptors showed more variability in expression between the strains. The PDGF A-chain mRNA induction was also decreased or absent in late passage human fibroblasts (senescent cells) when compared with early passage cells. These data suggest that the PDGF A-chain mRNA induction is regulated by an age related mechanism in human fibroblasts.
Insights
Platelet-derived growth factor (PDGF) A-chain mRNA induction decreases with donor age in human fibroblasts. This age-related decline suggests a mechanism impacting cellular responses over time.
Area of Science:
- Cellular and Molecular Biology
- Aging Research
- Fibroblast Biology
Background:
- Fibroblast stimulation with growth factors like PDGF or EGF can induce PDGF A-chain mRNA and PDGF-AA protein synthesis.
- This induction may indicate an autocrine feedback loop amplifying mitogenic signals.
- The influence of donor age and cellular replicative capacity on this feedback mechanism is not fully understood.
Purpose of the Study:
- To investigate the correlation between donor age, replicative capacity, and PDGF-BB-mediated PDGF A-chain induction in human fibroblasts.
- To characterize PDGF receptor expression and binding properties in fibroblasts from donors of varying ages.
Main Methods:
- Fibroblast cell strains from embryonic, neonatal, and old donors were utilized.
- PDGF A-chain mRNA induction was measured following PDGF-BB stimulation.
- PDGF alpha- and beta-receptor expression and binding were analyzed in different cell strains.
Main Results:
- PDGF A-chain induction was significantly reduced in fibroblasts from old donors compared to younger donors.
- PDGF beta-receptor expression was enhanced in older donor cell strains.
- PDGF A-chain mRNA induction was decreased or absent in senescent (late passage) fibroblasts.
Conclusions:
- Human fibroblast PDGF A-chain mRNA induction is subject to an age-related regulatory mechanism.
- Cellular senescence is associated with impaired PDGF A-chain mRNA induction.
- Age-associated changes in PDGF receptor expression may contribute to altered cellular responses.