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Lung defects in neonatal and adult stromal-derived factor–1 conditional knockout mice

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Abstract

Stromal-derived factor (SDF)-1/CXCL12 is a cytokine that is involved in organogenesis, hematopoiesis, chemoattraction, and wound healing. An SDF-1 knockout mouse (SDF-1-/-) has provided important insights into the role of SDF-1 in fetal development. Because the SDF-1 knockout is lethal in the perinatal period, we have created a conditional SDF-1 knockout mouse. In the present study, we induced conditionally knocked out SDF-1 in neonatal mice and found that lung development was compromised; neonatal lungs showed increased alveolar airspace and abnormal ultrastructure. Conditional knockout of SDF-1 in adult mice resulted in an emphysemic morphology, with increased alveolar airspace and thickened alveolar septa. Fluorescence angiography showed pulmonary vessel hyperdilation. To determine whether the hyperdilation involved nitric oxide, we inhibited endothelial nitric oxide synthase (eNOS) with N (G)-nitro-L- arginine methyl ester. This resulted in the inhibition of pulmonary vessel hyperdilation. Western blot results showed increased phosphorylation of eNOS in our induced SDF-1 knockout mice, indicating that eNOS is normally repressed in the presence of SDF-1, and that activation of eNOS contributes to pulmonary pathology. Thus, a conditional knockout mouse has been successsfully created for SDF-1; initial characterization indicates that SDF-1 is intimately involved in lung development and physiology.

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Acknowledgements

We thank Wei-Shuan Lin, Kuo-Jen Yen, and Ming-Chich Hsu for data processing, Wei-Sheng Tien for manuscript preparation, and Drs. Teh-Ying Chou and Hung Chiang for making constructive comments with regard to the manuscript.

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Authors and Affiliations

  1. Institute of Biochemistry and Molecular Biology, National Yang-Ming University, 155, Sec. 2, Li-Nong Street, Pei-Tou, Taipei, 11221, Taiwan

    Wen-Cheng Chen, Yi-Shiuan Tzeng, Hung Li & Ying-Chieh Tsai

  2. Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan

    Wen-Cheng Chen, Yi-Shiuan Tzeng, Hung Li, Wei-Sheng Tien & Ying-Chieh Tsai

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  1. Wen-Cheng Chen
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  2. Yi-Shiuan Tzeng
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  3. Hung Li
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  4. Wei-Sheng Tien
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  5. Ying-Chieh Tsai
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Correspondence to Ying-Chieh Tsai.

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Wen-Cheng Chen and Yi-Shiuan Tzeng contributed equally to this work.

This work was supported, in part, by research grants from the Chen-Han Foundation for Education, Academia Sinica (94 M003) and the National Science Council (NSC95-2314-B-303-003).

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Chen, WC., Tzeng, YS., Li, H. et al. Lung defects in neonatal and adult stromal-derived factor–1 conditional knockout mice. Cell Tissue Res 342, 75–85 (2010). https://doi.org/10.1007/s00441-010-1035-z

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  • DOI: https://doi.org/10.1007/s00441-010-1035-z

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