title: Conditional Knockout of Telomerase Reverse Transcriptase in Mesenchymal Cells Impairs Mouse Pulmonary Fibrosis.
abstract: Telomerase is typically expressed in cellular populations capable of extended replication, such as germ cells, tumor cells, and stem cells, but is also induced in tissue injury, repair and fibrosis. Its catalytic component, telomerase reverse transcriptase (TERT) is induced in lung fibroblasts from patients with fibrotic interstitial lung disease and in rodents with bleomycin-induced pulmonary fibrosis. To evaluate the fibroblast specific role of TERT in pulmonary fibrosis, transgenic mice bearing a floxed TERT allele were generated, and then crossed with an inducible collagen α2(I)-Cre mouse line to generate fibroblast specific TERT conditional knockout mice. TERT-specific deficiency in mesenchymal cells caused attenuation of pulmonary fibrosis as manifested by reduced lung hydroxyproline content, type I collagen and α-smooth muscle actin mRNA levels. The TERT-deficient mouse lung fibroblasts displayed decreased cell proliferative capacity and higher susceptibility to induced apoptosis compared with control cells. Additionally TERT deficiency was associated with heightened α-smooth muscle actin expression indicative of myofibroblast differentiation. However the impairment of cell proliferation and increased susceptibility to apoptosis would cause a reduction in the myofibroblast progenitor population necessary to mount a successful myofibroblast-dependent fibrotic response. These findings identified a key role for TERT in fibroblast proliferation and survival essential for pulmonary fibrosis.
authors.affiliation: Department of Pathology, University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America.
authors.forename: Tianju
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Pathology, University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America.
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Pathology, University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America.
authors.forename: Lin
authors.initials: L
authors.lastname: Ding
authors.affiliation: Department of Pathology, University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Pathology, University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America.
authors.forename: Francina
authors.initials: F
authors.lastname: Gonzalez De Los Santos
authors.affiliation: Department of Pathology, University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pathology, University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America.
authors.forename: Matthew
authors.initials: M
authors.lastname: Ullenbruch
authors.affiliation: Department of Pathology, University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America.
authors.forename: Biao
authors.initials: B
authors.lastname: Hu
authors.affiliation: Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Martins
authors.affiliation: Department of Pathology, University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America.
authors.forename: Sem H
authors.initials: SH
authors.lastname: Phan
mesh_terms: D000818:Animals; D059630:Mesenchymal Stem Cells / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011658:Pulmonary Fibrosis / Q000473:pathology*; D019098:Telomerase / Q000235:genetics*
chemical_list: D019098:Telomerase; C509187:Tert protein, mouse