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Telomerase expression restores dermal integrity to in vitro-aged fibroblasts in a reconstituted skin model.
- Source :
-
Experimental cell research [Exp Cell Res] 2000 Aug 01; Vol. 258 (2), pp. 270-8. - Publication Year :
- 2000
-
Abstract
- The lifespan of human fibroblasts and other primary cell strains can be extended by expression of the telomerase catalytic subunit (hTERT). Since replicative senescence is accompanied by substantial alterations in gene expression, we evaluated characteristics of in vitro-aged dermal fibroblast populations before and after immortalization with telomerase. The biological behavior of these populations was assessed by incorporation into reconstituted human skin. Reminiscent of skin in the elderly, we observed increased fragility and subepidermal blistering with increased passage number of dermal fibroblasts, but the expression of telomerase in late passage populations restored the normal nonblistering phenotype. DNA microarray analysis showed that senescent fibroblasts express reduced levels of collagen I and III, as well as increased levels of a series of markers associated with the destruction of dermal matrix and inflammatory processes, and that the expression of telomerase results in mRNA expression patterns that are substantially similar to early passage cells. Thus, telomerase activity not only confers replicative immortality to skin fibroblasts, but can also prevent or reverse the loss of biological function seen in senescent cell populations.<br /> (Copyright 2000 Academic Press.)
- Subjects :
- Catalytic Domain
Cell Line
Cells, Cultured
DNA-Binding Proteins
Dermis cytology
Dermis metabolism
Fibroblasts cytology
Gene Expression Regulation
Humans
Keratinocytes cytology
Keratinocytes physiology
Models, Biological
Physical Stimulation
Telomerase biosynthesis
Telomerase genetics
Cellular Senescence physiology
Dermis physiology
Fibroblasts physiology
RNA
Skin Physiological Phenomena
Telomerase physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0014-4827
- Volume :
- 258
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Experimental cell research
- Publication Type :
- Academic Journal
- Accession number :
- 10896778
- Full Text :
- https://doi.org/10.1006/excr.2000.4945