Alterations in pulmonary mRNA encoding procollagens, fibronectin and transforming growth factor-beta precede bleomycin-induced pulmonary fibrosis in mice.
Alterations in pulmonary mRNA encoding procollagens, fibronectin and transforming growth factor-beta precede bleomycin-induced pulmonary fibrosis in mice.
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发表时间：
1988-08
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通讯作者：
D. Hoyt;J. Lazo
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作者：
D. Hoyt;J. Lazo
持续皮下治疗的雌性 C57Bl/6 小鼠每公斤体重输注 100 毫克博莱霉素 1 周，比 BALB/c 小鼠出现更明显的肺纤维化。博莱霉素治疗后 4 周内，肺部编码纤连蛋白、α2I 前胶原和 α1III 前胶原的 mRNA 含量增加。与 BALB/c 小鼠相比，C57Bl/6 小鼠的增加幅度更大且发生更早。纤连蛋白 mRNA 在 C57Bl/6 小鼠中增加了 12 倍，在 BALB/c 小鼠中仅增加了 3 倍，而 α1III 前胶原 mRNA 在 C57Bl/6 小鼠中增加了 4 倍，在 BALB/c 小鼠中增加了 2 倍。 α2I 前胶原 mRNA 仅在 C57Bl/6 小鼠中增加（2 倍）。 C57Bl/6 小鼠中的增加是连续的：纤连蛋白 mRNA 首先升高，然后是 α2I 前胶原，然后是 α1III 前胶原 mRNA。这些 mRNA 升高和细胞外基质积累之间的时间关系以及 C57Bl/6 小鼠中的夸大反应表明基质积累是 mRNA 水平的函数。治疗1周后，C57Bl/6小鼠中转化生长因子-β mRNA相对于总聚腺苷酸化RNA升高了5倍，而BALB/c小鼠中则降低了80%。转化生长因子-β mRNA 的早期改变可能导致博莱霉素诱导的肺纤维化的小鼠品系变异，并表明转化生长因子-β 参与了这种疾病。
Female C57Bl/6 mice treated by constant s.c. infusion for 1 week with 100 mg of bleomycin per kg of body weight develop a more pronounced pulmonary fibrosis than BALB/c mice. Within 4 weeks after bleomycin treatment, the pulmonary content of mRNAs encoding fibronectin, alpha 2I procollagen and alpha 1III procollagen was increased. The increases were greater and occurred earlier in C57Bl/6 mice compared to BALB/c mice. Fibronectin mRNA increased 12-fold in C57Bl/6 mice and only 3-fold in BALB/c mice, whereas alpha 1III procollagen mRNA increased 4-fold in C57Bl/6 mice and 2-fold in BALB/c mice. alpha 2I procollagen mRNA was increased only in C57Bl/6 mice (2-fold). The increases were sequential in C57Bl/6 mice: fibronectin mRNA was elevated first, followed by alpha 2I procollagen, then alpha 1III procollagen mRNA. The temporal relationship between these mRNA elevations and extracellular matrix accumulation, and the exaggerated responses in C57Bl/6 mice, suggest that matrix accumulation is a function of the mRNA levels. Transforming growth factor-beta mRNA relative to total polyadenylated RNA was elevated 5-fold in C57Bl/6 mice and depressed 80% in BALB/c mice 1 week after treatment. Early alterations in transforming growth factor-beta mRNA may contribute to murine strain variation in bleomycin-induced pulmonary fibrosis and suggest the involvement of transforming growth factor-beta in this disease.