Am. J. Respir. Cell Mol. Biol., Volume 26, Number 5, May, 2002 534-540

Regulation of Telomerase Activity in Rat Lung Fibroblasts

Tianju Liu, Yasuhiro Nozaki, and Sem H. Phan

Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan

Fibroblasts from bleomycin-injured lungs express telomerase activity transiently during the period of active fibrosis, but the signal(s) responsible for its induction is (are) unknown. The objective of this study was to identify potential mediators capable of regulating telomerase activity induction in rat lung fibroblasts during pulmonary fibrosis. Lung fibroblasts from control (NRF) and bleomycin-treated (BRF) rats were isolated and treated in vitro with either basic fibroblast growth factor (bFGF) or interleukin-4 (IL-4). At selected time points after treatment, the cells were analyzed for telomerase activity, as well as telomerase reverse transcriptase (TERT) mRNA and protein by reverse transcriptase/polymerase chain reaction and Western blot, respectively. The results showed that bFGF could induce telomerase activity in NRF and stimulate further the induced activity in BRF. The bFGF effect was accompanied by increased TERT protein expression and a rapid but transient increase in TERT mRNA. In contrast, IL-4 inhibited the induced telomerase activity in BRF, which was accompanied by increased -smooth muscle actin expression, an indicator of myofibroblast differentiation. These findings suggest that telomerase expression could be induced in rat lung fibroblasts by bFGF, but suppressed by IL-4, which promoted myofibroblast differentiation. The latter is consistent with the preferential expression of telomerase activity in fibroblasts relative to myofibroblasts.

This article has been cited by other articles:

				S. H. Phan Biology of Fibroblasts and Myofibroblasts Proceedings of the ATS, April 15, 2008; 5(3): 334 - 337. [Abstract] [Full Text] [PDF]

				H. LI and J.-P. LIU Mechanisms of Action of TGF-beta in Cancer: Evidence for Smad3 as a Repressor of the hTERT Gene Ann. N.Y. Acad. Sci., October 1, 2007; 1114(1): 56 - 68. [Abstract] [Full Text] [PDF]

				D. Kass, R. S. Bridges, A. Borczuk, and S. Greenberg Methionine Aminopeptidase-2 as a Selective Target of Myofibroblasts in Pulmonary Fibrosis Am. J. Respir. Cell Mol. Biol., August 1, 2007; 37(2): 193 - 201. [Abstract] [Full Text] [PDF]

				S. L. Schissel and M. D. Layne Telomerase, myofibroblasts, and pulmonary fibrosis. Am. J. Respir. Cell Mol. Biol., May 1, 2006; 34(5): 520 - 522. [Full Text] [PDF]

				T. Liu, B. Hu, M. J. Chung, M. Ullenbruch, H. Jin, and S. H. Phan Telomerase Regulation of Myofibroblast Differentiation Am. J. Respir. Cell Mol. Biol., May 1, 2006; 34(5): 625 - 633. [Abstract] [Full Text] [PDF]

				V. N. Lama and S. H. Phan The extrapulmonary origin of fibroblasts: stem/progenitor cells and beyond. Proceedings of the ATS, January 1, 2006; 3(4): 373 - 376. [Abstract] [Full Text] [PDF]

				L Gomez-Garcia, F M Sanchez, M T Vallejo-Cremades, I A G. de Segura, and E De Miguel del Campo Direct activation of telomerase by GH via phosphatidylinositol 3'-kinase J. Endocrinol., June 1, 2005; 185(3): 421 - 428. [Abstract] [Full Text] [PDF]

				Y. Yang, X. Zhe, S. H. Phan, M. Ullenbruch, and L. Schuger Involvement of Serum Response Factor Isoforms in Myofibroblast Differentiation During Bleomycin-Induced Lung Injury Am. J. Respir. Cell Mol. Biol., November 1, 2003; 29(5): 583 - 590. [Abstract] [Full Text]

				N. Kaminski, J. A. Belperio, P. B. Bitterman, L. Chen, S. W. Chensue, A. M.K. Choi, S. Dacic, J. H. Dauber, R. M. du Bois, J. J. Enghild, et al. Idiopathic Pulmonary Fibrosis Am. J. Respir. Cell Mol. Biol., September 1, 2003; 29(3): S1 - 105. [Full Text] [PDF]

				D. J. Kurz, Y. Hong, E. Trivier, H.-L. Huang, S. Decary, G. H. Zang, T. F. Luscher, and J. D. Erusalimsky Fibroblast Growth Factor-2, But Not Vascular Endothelial Growth Factor, Upregulates Telomerase Activity in Human Endothelial Cells Arterioscler. Thromb. Vasc. Biol., May 1, 2003; 23(5): 748 - 754. [Abstract] [Full Text] [PDF]

				S. Roy, S. Khanna, A. A. Bickerstaff, S. V. Subramanian, M. Atalay, M. Bierl, S. Pendyala, D. Levy, N. Sharma, M. Venojarvi, et al. Oxygen Sensing by Primary Cardiac Fibroblasts: A Key Role of p21Waf1/Cip1/Sdi1 Circ. Res., February 21, 2003; 92(3): 264 - 271. [Abstract] [Full Text] [PDF]

				L. J. Mauro and D. N. Foster Regulators of Telomerase Activity Am. J. Respir. Cell Mol. Biol., May 1, 2002; 26(5): 521 - 524. [Full Text] [PDF]