Radiation-induced production of PAR-1 and TGF-beta 1 mRNA in lung of C57Bl6 and C3H murine strains and influence of pharmacoprophylaxis by ACE inhibitors.
Transforming growth factor beta 1 (TGF-beta1) plays an important role in the development of radiation- and drug-induced organ diseases. Proteinases-activated receptor 1 (PAR-1) is involved in many pathophysiologic processes after its activation by serine proteases. The aim of the present study was to determine messenger RNA (mRNA) production of TGF-beta1 and PAR-1 in the lungs after local irradiation. Mice of C57BL/6 and C3H/J strains with different susceptibility to fibrosis development were exposed to a of 15Gy. Non-irradiated mice of both strains were used as negative controls. Control (irradiated) and irradiated angiotensin-converting enzyme (ACE) inhibitor-treated animals were examined simultaneously. The ACE inhibitor group was given butylaminiperindopril for 9 days after irradiation (15Gy) at a daily dose of 0.1 or 0.2mg/kg per rectum. On day 9, all mice were sacrificed, and the production of mRNA TGF-beta1 and PAR-1 in lung tissue was determined semiquantitatively using reverse transcriptase polymerase chain reaction, and immunohistochemical analysis of PAR-1 expression in pulmonary tissue was performed. In the fibrosing murine strain C57Bl/6, there was an increase in the mRNA TGF-beta1 and PAR-1 levels in lungs 9 days after irradiation as compared with non-irradiated controls and non-fibrosing murine strain C3H/J. In butylaminiperindopril-treated mice, a decrease in transcript of TGF-beta1 and PAR-1 was observed. Thus, PAR-1 is involved in radiation-induced lung fibrosis in correlation with TGF-beta1 production. Administration of ACEI influences PAR-1 and TGF-beta1 expression.
Matej
Radoslav
R
Department of Pathology, Thomayer Teaching Hospital, Vídenská 800, Prague 4 - Krc, 14059 Prague, Czech Republic. radoslav.matej@ftn.cz <radoslav.matej@ftn.cz>
Housa
Daniel
D
Poucková
Pavla
P
Zadinová
Marie
M
Olejár
Tomás
T
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D005260:Female; D005720:Gamma Rays / Q000009:adverse effects; D007124:Immunoenzyme Techniques; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D020913:Perindopril / Q000627:therapeutic use; D011658:Pulmonary Fibrosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism*; D011833:Radiation Injuries, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011837:Radiation-Protective Agents / Q000627:therapeutic use; D044463:Receptor, PAR-1 / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D012333:RNA, Messenger; D011837:Radiation-Protective Agents; D044463:Receptor, PAR-1; D016212:Transforming Growth Factor beta; D020913:Perindopril