Telomerase activity in bleomycin-induced epithelial cell apoptosis and lung fibrosis.
Epithelial cell injury and apoptosis are recognised as early features in idiopathic pulmonary fibrosis and bleomycin-induced fibrosis in mice. Telomerase is a known apoptosis-alleviating factor. The role of telomerase was studied during bleomycin-induced lung epithelial cell (LEC) apoptosis in vitro in a mouse LEC line, and in vivo in LECs isolated from bleomycin-treated mice. The current authors evaluated changes in murine telomerase reverse transcriptase (mTERT) mRNA levels and changes in telomerase activity with the TRAPeze Detection Kit, telomeric length with the TeloTTAGGG Telomere Length Kit, and LEC apoptosis with FACScan and 4,6-diamino-2-phenylindole dihydrochloride stain. There was a significant elevation in mTERT mRNA and a transient 41% increase in telomerase activity 24 h after in vitro bleomycin treatment. At 72 h, telomerase activity had fallen to 26% below levels in untreated cells. Reduction of telomerase activity over time, or by direct inhibition, significantly elevated LEC apoptosis. No change in average telomeric length was noted. In vivo, telomerase activity of LECs from bleomycin-treated mice increased at 7 and 14 days. In conclusion, telomerase activity may play a protective role against robust bleomycin-induced lung epithelial cell apoptosis. Moreover, stabilising telomerase activity may decrease epithelial cell apoptosis and the resulting lung fibrosis.
Fridlender
Z G
ZG
Lung Cellular and Molecular Biology Laboratory, Institute of Pulmonary Medicine, Hadassah - Hebrew University Medical Center, Jerusalem, Israel. fridlender@hadassah.org.il.
Cohen
P Y
PY
Golan
O
O
Arish
N
N
Wallach-Dayan
S
S
Breuer
R
R
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001761:Bleomycin / Q000633:toxicity; D016009:Chi-Square Distribution; D004790:Enzyme Induction; D004847:Epithelial Cells / Q000201:enzymology* / Q000473:pathology; D005434:Flow Cytometry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D019098:Telomerase / Q000378:metabolism*
D012333:RNA, Messenger; D001761:Bleomycin; D019098:Telomerase