Influence of Telomerase Expression on Cell Cycle Proteins, Type I Collagen and Interstitial Collagenase in Human Dermal Fibroblasts

Abstract

Telomere shortening has been implicated as an important mechanism that drives somatic cells into termination of cellular division and finally into cellular senescence. However, in germ line cells and tumor cells, which show distinct characteristics of ceaseless celluelar division without entering cellular senescence, the presence of telomerase prevents the telomere shortening. The expression of the catalytic subunit of human telomerase in normal human fibroblasts allows them to escape replicative senescence. In this study, we expressed hTERT in human neonatal foreskin fibroblasts(NFB-hTERT) and investigated the influence of hTERT on the cell cycle and metabolism of type I collagen. With increased passage, the NFB-hTERT cells showed down-regulation of p16 and cyclin D1 levels while the expression of CDK4 did not change. The basal level of type I collagen decreased with increased passage in NFB but the level did not change in NFB-hTERT. Basal level of matrix metalloproteinase-1 was reduced in aging NFB and NFB-hTERT and treatment of TNF- resulted in less induction in NFB-hTERT. These results suggest the mechanism of inhibition of senescence by hTERT in human dermal fibroblasts.