First Author | Xu J | Year | 2007 |
Journal | Am J Respir Cell Mol Biol | Volume | 37 |
Issue | 3 | Pages | 291-9 |
PubMed ID | 17463394 | Mgi Jnum | J:138491 |
Mgi Id | MGI:3805240 | Doi | 10.1165/rcmb.2006-0187OC |
Citation | Xu J, et al. (2007) Role of the SDF-1/CXCR4 axis in the pathogenesis of lung injury and fibrosis. Am J Respir Cell Mol Biol 37(3):291-9 |
abstractText | Stromal cell-derived factor-1 (SDF-1) participates in mobilizing bone marrow-derived stem cells, via its receptor CXCR4. We studied the role of the SDF-1/CXCR4 axis in a rodent model of bleomycin-induced lung injury in C57BL/6 wild-type and matrix metalloproteinase (MMP)-9 knockout mice. After intratracheal instillation of bleomycin, SDF-1 levels in serum and bronchial alveolar lavage fluid increased. These changes were accompanied by increased numbers of CXCR4(+) cells in the lung and a decrease in a population of CXCR4(+) cells in the bone marrow that did not occur in MMP-9(-)/(-) mice. Both SDF-1 and lung lysates from bleomycin-treated mice induced migration of bone marrow-derived stem cells in vitro that was blocked by a CXCR4 antagonist, TN14003. Treatment of mice with TN14003 with bleomycin-induced lung injury significantly attenuated lung fibrosis. Lung tissue from patients with idiopathic pulmonary fibrosis had higher numbers of cells expressing both SDF-1 and CXCR4 than did normal lungs. Our data suggest that the SDF-1/CXCR4 axis is important in the complex sequence of events triggered by bleomycin exposure that eventuates in lung repair. SDF-1 participates in mobilizing bone marrow-derived stem cells, via its receptor CXCR4. |