Telomerase regulation of myofibroblast differentiation.
Telomerase activity, which has wide expression in cancerous cells, is induced in lung proliferating fibroblasts. It is preferentially expressed in fibroblasts versus myofibroblasts. It is unknown whether regulation of telomerase expression is related to the process of fibroblast differentiation into myofibroblasts. The objective of this study was to clarify such a potential link between telomerase expression and myofibroblast differentiation. Telomerase inhibitor, 3'-azido-2',3'-dideoxythymidine, or antisense oligonucleotide to the telomerase RNA component was used to inhibit the induced fibroblast telomerase activity. The results showed that inhibition of induced telomerase increased alpha-smooth muscle actin expression, an indicator of myofibroblast differentiation. In contrast, induction of telomerase by basic fibroblast growth factor inhibited alpha-smooth muscle actin expression. These findings suggest that the loss of telomerase activity is closely associated with myofibroblast differentiation and possibly functions as a trigger for myofibroblast differentiation. Conversely, expression of telomerase suppresses myofibroblast differentiation.
Liu
Tianju
T
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Hu
Biao
B
Chung
Myoung Ja
MJ
Ullenbruch
Matt
M
Jin
Hong
H
Phan
Sem H
SH
D000199:Actins / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001761:Bleomycin / Q000494:pharmacology; D002454:Cell Differentiation; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects; D008168:Lung / Q000166:cytology / Q000187:drug effects; D032342:Muscle Cells / Q000166:cytology* / Q000187:drug effects; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012313:RNA / Q000037:antagonists & inhibitors; D051381:Rats; D011916:Rats, Inbred F344; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors; D015215:Zidovudine / Q000494:pharmacology
D000199:Actins; D001761:Bleomycin; D004268:DNA-Binding Proteins; D016376:Oligonucleotides, Antisense; D012313:RNA; D019098:Telomerase; D013873:Thionucleotides; D015215:Zidovudine; C498862:Acta2 protein, rat; C422952:telomerase RNA