title: Telomerase activity is required for bleomycin-induced pulmonary fibrosis in mice.
abstract: In addition to its well-known expression in the germline and in cells of certain cancers, telomerase activity is induced in lung fibrosis, although its role in this process is unknown. To identify the pathogenetic importance of telomerase in lung fibrosis, we examined the effects of telomerase reverse transcriptase (TERT) deficiency in a murine model of pulmonary injury. TERT-deficient mice showed significantly reduced lung fibrosis following bleomycin (BLM) insult. This was accompanied by a significant reduction in expression of lung alpha-SMA, a marker of myofibroblast differentiation. Furthermore, lung fibroblasts isolated from BLM-treated TERT-deficient mice showed significantly decreased proliferation and increased apoptosis rates compared with cells isolated from control mice. Transplantation of WT BM into TERT-deficient mice restored BLM-induced lung telomerase activity and fibrosis to WT levels. Conversely, transplantation of BM from TERT-deficient mice into WT recipients resulted in reduced telomerase activity and fibrosis. These findings suggest that induction of telomerase in injured lungs may be caused by BM-derived cells, which appear to play an important role in pulmonary fibrosis. Moreover, TERT induction is associated with increased survival of lung fibroblasts, which favors the development of fibrosis instead of injury resolution.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109-2200, USA.
authors.forename: Tianju
authors.initials: T
authors.lastname: Liu
authors.forename: Myoung Ja
authors.initials: MJ
authors.lastname: Chung
authors.forename: Matthew
authors.initials: M
authors.lastname: Ullenbruch
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Yu
authors.forename: Hong
authors.initials: H
authors.lastname: Jin
authors.forename: Biao
authors.initials: B
authors.lastname: Hu
authors.forename: Yoon Young
authors.initials: YY
authors.lastname: Choi
authors.forename: Fuyuki
authors.initials: F
authors.lastname: Ishikawa
authors.forename: Sem H
authors.initials: SH
authors.lastname: Phan
mesh_terms: D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001761:Bleomycin / Q000633:toxicity*; D016026:Bone Marrow Transplantation; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004790:Enzyme Induction / Q000187:drug effects / Q000235:genetics; D005347:Fibroblasts / Q000201:enzymology* / Q000473:pathology; D008168:Lung / Q000201:enzymology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D000903:Antibiotics, Antineoplastic; D000943:Antigens, Differentiation; D001761:Bleomycin; D019098:Telomerase; C509187:Tert protein, mouse