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Research ArticlePulmonology Free access | 10.1172/JCI32369

Telomerase activity is required for bleomycin-induced pulmonary fibrosis in mice

Tianju Liu,1 Myoung Ja Chung,1 Matthew Ullenbruch,1 Hongfeng Yu,1 Hong Jin,1 Biao Hu,1 Yoon Young Choi,1 Fuyuki Ishikawa,2 and Sem H. Phan1

1Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA. 2Laboratory of Cell Cycle Regulation, Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.

Address correspondence to: Sem H. Phan, Department of Pathology, University of Michigan Medical School, Med. Sci. I, Room 4204, Box 0602, Ann Arbor, Michigan 48109-2200, USA. Phone: (734) 647-8153; Fax: (734) 615-2331; E-mail: shphan@umich.edu.

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1Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA. 2Laboratory of Cell Cycle Regulation, Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.

Address correspondence to: Sem H. Phan, Department of Pathology, University of Michigan Medical School, Med. Sci. I, Room 4204, Box 0602, Ann Arbor, Michigan 48109-2200, USA. Phone: (734) 647-8153; Fax: (734) 615-2331; E-mail: shphan@umich.edu.

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1Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA. 2Laboratory of Cell Cycle Regulation, Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.

Address correspondence to: Sem H. Phan, Department of Pathology, University of Michigan Medical School, Med. Sci. I, Room 4204, Box 0602, Ann Arbor, Michigan 48109-2200, USA. Phone: (734) 647-8153; Fax: (734) 615-2331; E-mail: shphan@umich.edu.

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1Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA. 2Laboratory of Cell Cycle Regulation, Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.

Address correspondence to: Sem H. Phan, Department of Pathology, University of Michigan Medical School, Med. Sci. I, Room 4204, Box 0602, Ann Arbor, Michigan 48109-2200, USA. Phone: (734) 647-8153; Fax: (734) 615-2331; E-mail: shphan@umich.edu.

Find articles by Yu, H. in: PubMed | Google Scholar

1Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA. 2Laboratory of Cell Cycle Regulation, Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.

Address correspondence to: Sem H. Phan, Department of Pathology, University of Michigan Medical School, Med. Sci. I, Room 4204, Box 0602, Ann Arbor, Michigan 48109-2200, USA. Phone: (734) 647-8153; Fax: (734) 615-2331; E-mail: shphan@umich.edu.

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1Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA. 2Laboratory of Cell Cycle Regulation, Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.

Address correspondence to: Sem H. Phan, Department of Pathology, University of Michigan Medical School, Med. Sci. I, Room 4204, Box 0602, Ann Arbor, Michigan 48109-2200, USA. Phone: (734) 647-8153; Fax: (734) 615-2331; E-mail: shphan@umich.edu.

Find articles by Hu, B. in: PubMed | Google Scholar

1Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA. 2Laboratory of Cell Cycle Regulation, Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.

Address correspondence to: Sem H. Phan, Department of Pathology, University of Michigan Medical School, Med. Sci. I, Room 4204, Box 0602, Ann Arbor, Michigan 48109-2200, USA. Phone: (734) 647-8153; Fax: (734) 615-2331; E-mail: shphan@umich.edu.

Find articles by Choi, Y. in: PubMed | Google Scholar

1Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA. 2Laboratory of Cell Cycle Regulation, Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.

Address correspondence to: Sem H. Phan, Department of Pathology, University of Michigan Medical School, Med. Sci. I, Room 4204, Box 0602, Ann Arbor, Michigan 48109-2200, USA. Phone: (734) 647-8153; Fax: (734) 615-2331; E-mail: shphan@umich.edu.

Find articles by Ishikawa, F. in: PubMed | Google Scholar

1Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA. 2Laboratory of Cell Cycle Regulation, Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.

Address correspondence to: Sem H. Phan, Department of Pathology, University of Michigan Medical School, Med. Sci. I, Room 4204, Box 0602, Ann Arbor, Michigan 48109-2200, USA. Phone: (734) 647-8153; Fax: (734) 615-2331; E-mail: shphan@umich.edu.

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Published November 15, 2007 - More info

J Clin Invest. https://doi.org/10.1172/JCI32369.
© 2007 The American Society for Clinical Investigation
Published November 15, 2007 - Version history
Received: April 11, 2007; Accepted: September 12, 2007
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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 α-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.

Version history
  • Version 1 (November 15, 2007): No description
  • Version 3 (December 3, 2007): No description
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