Telomere maintenance attenuates liver fibrosis in mouse models

Researchers investigated whether telomere dysfunction contributes to hepatic stellate cell activation during liver fibrogenesis. Fibrosis was induced in mice using carbon tetrachloride or bile duct ligation and assessed through tissue and molecular pathology and biochemistry. Interventions included stellate cell–specific overexpression of telomerase reverse transcriptase (TERT) or Acd, which encodes the shelterin component TPP1, and intraperitoneal administration of TELODIN, a D-amino acid octapeptide that stabilizes TPP1.

TERT overexpression alleviated fibrosis while suppressing stellate cell activation, proliferation, and transdifferentiation. TPP1 overexpression similarly mitigated fibrosis and prevented telomere dysfunction and shortening. TELODIN stabilized TPP1, reduced telomere dysfunction, and maintained stellate cell quiescence, limiting conversion into profibrotic myofibroblasts. The supplied report does not provide animal numbers, quantitative effect sizes, or statistical estimates.

These findings support telomere maintenance as a potential therapeutic target in experimental hepatic fibrosis. However, the evidence is confined to mouse models; it does not establish efficacy, safety, or a clinically applicable dosing strategy in patients with liver fibrosis or cirrhosis.