Warshamana G Sakuntala, Pociask Derek A, Sime Patricia, Schwartz David A, Brody Arnold R
Lung Biology Program, Department of Pathology, Tulane University Health Sciences Center, New Orleans, Louisiana 70112-2699, USA.
Am J Respir Cell Mol Biol. 2002 Dec;27(6):705-13. doi: 10.1165/rcmb.2002-0096OC.
Pulmonary fibrosis (PF) is caused by a number of inhaled agents, as well as by some drugs and toxic particles. The elaboration of certain peptide growth factors is thought to be key to the development of this disease process. In addition, genetic susceptibility plays a role in the development of PF. For instance, we have previously shown that the 129J strain of mice is resistant, whereas the C57BL/6 strain is highly susceptible, to asbestos-induced fibrosis. To pursue this further, in one mouse model, we crossed the 129J strain to the C57BL/6 strain to produce an F1 generation and subsequently backcrossed the F1 mice to the inbred founders. This backcross to the 129 inbred strain produced reverse similar 25% of the offspring with a phenotype that was protected from the fibrogenic effects of inhaled asbestos fibers. In the second model, both strains of mice were treated intratracheally with an adenovirus vector (AdV), which transduces expression of active transforming growth factor (TGF)-beta(1) in the lungs, producing fibroproliferative lung disease. Compared with C57 mice, a significant number of 129 strain mice exhibited at least a 1-wk delay in the fibroproliferative response to TGF-beta(1) expression at three concentrations of virus. These findings suggest that certain sequences in a gene or a cluster of genes in the 129 mouse strain impart a phenotype in which there is a delay in, or protection from, the development of lung fibrogenesis.
肺纤维化（PF）由多种吸入剂以及某些药物和有毒颗粒引起。某些肽生长因子的产生被认为是该疾病进程发展的关键。此外，遗传易感性在PF的发展中起作用。例如，我们之前已经表明，129J品系的小鼠对石棉诱导的纤维化具有抗性，而C57BL/6品系则高度敏感。为了进一步研究，在一个小鼠模型中，我们将129J品系与C57BL/6品系杂交产生F1代，随后将F1小鼠与近交系亲本回交。与129近交系的回交产生了约25%的具有保护其免受吸入石棉纤维致纤维化作用表型的后代。在第二个模型中，两种品系的小鼠均经气管内给予腺病毒载体（AdV），该载体在肺中转导活性转化生长因子（TGF）-β(1)的表达，从而产生纤维增生性肺病。与C57小鼠相比，在三种病毒浓度下，大量129品系小鼠对TGF-β(1)表达的纤维增生反应至少延迟1周。这些发现表明，129小鼠品系中一个基因或一组基因中的某些序列赋予了一种表型，即肺纤维化的发展延迟或受到保护。
