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Tenascin C is dysregulated in hypoplastic lungs of miR-200b−/− mice

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Abstract

Purpose

We previously demonstrated that absence of miR-200b results in abnormal lung development in congenital diaphragmatic hernia due to imbalance between epithelial and mesenchymal cells. Tenascin C is a highly conserved extracellular matrix protein involved in epithelial to mesenchymal transition, tissue regeneration and lung development. Considering the involvement of Tenascin C and miR-200b and their potential interaction, we aimed to study Tenascin C during lung development in the absence of miR-200b.

Methods

We collected lungs of miR-200b−/− mice (male, 8 weeks). We performed Western blot (WB) analysis (N = 6) and immunofluorescence (N = 5) for Tenascin C and alpha smooth muscle actin and RT-qPCR for Tenascin C gene expression (N = 4).

Results

Using WB analysis, we observed a decreased total protein abundance of Tenascin C in miR-200b−/− lungs (miR-200b+/+: 3.8 × 107 ± 1 × 107; miR-200b−/−: 1.9 × 107 ± 5 × 106; p = 0.002). Immunofluorescence confirmed decreased total Tenascin C in miR-200b−/− lungs. Tenascin C was significantly decreased in the mesenchyme but relatively increased in the airways of mutant lungs. Total lung RNA expression of Tenascin C was higher in miR-200b−/− lungs.

Conclusion

We report dysregulation of Tenascin C in lungs of miR-200b−/− mice. This suggests that absence of miR-200b results in abnormal Tenascin C abundance contributing to the lung hypoplasia observed in miR-200b−/− mice.

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Acknowledgements

Moritz Markel has a research scholarship (MA 8982/1-1) of the “Deutsche Forschungsgemeinschaft e.V.” (DFG—German Research Foundation); Dr. Richard Keijzer is the Thorlakson Chair in Surgical Research for the Department of Surgery and the University of Manitoba.

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Authors and Affiliations

  1. Division of Pediatric Surgery, Department of Surgery, Children’s Hospital Research Institute of Manitoba, University of Manitoba, AE402-820 Sherbrook Street, Winnipeg, MB, R3A 1S1, Canada

    Moritz Markel, Wai Hei Tse, Nolan DeLeon, Daywin Patel, Shana Kahnamouizadeh & Richard Keijzer

  2. Department of Pediatric Surgery, University of Leipzig, Leipzig, Germany

    Moritz Markel, Martin Lacher & Richard Wagner

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  1. Moritz Markel
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  2. Wai Hei Tse
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Correspondence to Richard Keijzer.

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Markel, M., Tse, W.H., DeLeon, N. et al. Tenascin C is dysregulated in hypoplastic lungs of miR-200b−/− mice. Pediatr Surg Int 38, 695–700 (2022). https://doi.org/10.1007/s00383-022-05096-0

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