Telomerase RNA component knockout is associated with iron accumulation and altered transferrin receptor 1 and ferroportin 1 expression in the liver and lung.

BACKGROUND AND OBJECTIVES: Based on the accumulated data, we hypothesized that telomerase activity may affect body iron metabolism. The aim of this study was to test this hypothesis. METHODS: We investigated the effect of telomerase RNA component (TERC) knockout on the following; telomere length, TERC and telomerase reverse transcriptase (TERT) expression; serum iron and iron-related indexes; liver and lung iron and ferritins, iron transporters, and iron regulatory molecule expression using early- (first-generation G1) and/or late-generation (third-generation G3) TERC-/- mice. RESULTS: We found that TERC-/- induces a significant reduction in serum iron and ferroportin1 (Fpn1) expression in the liver and lung; an increase in transferrin (Tf) and ferritin heavy or light chain (Ft-H or Ft-L) levels in serum; an increase in iron, Ft-H and/or Ft-L, transferrin receptor (TfR)1 and 2 expression in the liver and lung. We also observed that telomere length is gradually shortened and hepcidin expression is enhanced with increased TERC deletion and that TERT mRNA expression is significantly increased in the liver, but not the lung in TERC-/- mice. CONCLUSION: Our findings showed that TERC can significantly affect body iron metabolism as we hypothesized. The increased iron in the liver and the lung of TERC-/- mice may be due to increased TfR1 expression as well as reduced Fpn1 level via hepcidin pathways.