Procollagen gene expression is down-regulated by taurine and niacin at the transcriptional level in the bleomycin hamster model of lung fibrosis.
Taurine (T) and niacin (N) have previously been found to block the accumulation of collagen in the bleomycin (BL) model of interstitial pulmonary fibrosis. The present study was designed to evaluate whether the mechanism for the antifibrotic effect of combined treatment with taurine and niacin involves the down-regulation of BL-induced overexpression of procollagen I and III messenger ribonucleic acid (mRNA) levels in lungs. Hamsters were intratracheally instilled with three consecutive doses of saline or BL at weekly intervals (2.5, 2.0, 1.5 units/5 ml/kg). Four groups of animals were fed a diet throughout the experiment containing either 2.5% taurine and 2.5% niacin or the same diet without the drugs. The four groups were saline-instilled with the control diet (SA + CD), saline-instilled with TN in the diet (SA + TN), BL-instilled with the control diet (BL + CD), and BL-instilled with the TN diet (BL + TN). Steady state transcript levels in total RNA prepared from lungs of all four groups were determined at 0, 3, 7, 14 and 21 days after the last BL instillation by slot blot and Northern blot analyses. Results indicate that procollagen I mRNA levels are elevated compared with saline control by 2.5-, 2.4- and 2.0-fold at 7, 14, and 21 days after the last dose of BL instillation, respectively. Dietary treatment with taurine and niacin decreased the steady state level of BL-induced increases of procollagen I mRNA from day 0 through 21. We observed a similar pattern of procollagen III inhibition by taurine and niacin from day 3 through day 21. Transcription of procollagen I and III genes was readily detected in nuclei prepared from BL-treated lung samples at 14 days after treatment. In contrast, transcription of procollagen I and III genes was barely detectable in nuclei prepared at the same time point from BL + TN treated lungs. Our results suggest that procollagen I and III gene expression in BL-induced lung fibrosis in hamsters is transcriptionally down-regulated by combined treatment with taurine and niacin.
Gurujeyalakshmi
G
G
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, USA.
Iyer
S N
SN
Hollinger
M A
MA
Giri
S N
SN
D000818:Animals; D001761:Bleomycin / Q000633:toxicity; D003094:Collagen / Q000096:biosynthesis; D006224:Cricetinae; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D008647:Mesocricetus; D009525:Niacin / Q000494:pharmacology*; D011347:Procollagen / Q000235:genetics*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D013654:Taurine / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
D011347:Procollagen; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D001761:Bleomycin; D013654:Taurine; D009525:Niacin; D003094:Collagen