Our work on the role of the mechanical properties of the nuclear envelopment in Ventilator-Induced Lung Injury (VILI) has been published in Science Translational Medicine. More than 5 years of work have been finally exposed to the scientific community. We are very proud of the article, and happy to publish in such a great journal.
However, this article is the result of two concatenated errors that, in this case, led to a exciting finding.
We made the first error during our research on autophagy, inflammation and VILI, circa 2012, published in AJP-Lung. In that project, we started to obtain nuclear extracts to characterize the translocation of transcription factors by western blot. And, as a loading control, we tested Lamin-A. To our surprise, Lamin-A was not a good loading control, and mechanical ventilation caused a huge increase in its abundance.
The suspicion that Lamin-A could play a role in VILI persisted in the lab discussions for some years. And finally we decide to explore this path. After all, we have Zmpste24-knockout mice available. These animals show a fascinating phenotype, with most of the symptoms of accelerated aging and in line with other laminopathies. Therefore, we expected this fragile animals to be more susceptible to VILI. This was our second error.
To our surprise, these animals were resistant to mechanical stretch. We had to repeat the experiments several times until we were sure that finding was not an artefact. So aging, a condition that increases susceptibility to VILI, was not involved. From then, we explored the role of Lamin-A in nuclear mechanics, following this amazing paper from Swift and coworkers. Then came the micropipette aspiration experiments, characterization of different mouse models and genotypes, human samples…
And, more important, the strong conviction that nuclear and cell mechanics are key players in the finding of a specific treatment of VILI (keeping inflammation intact!).
crit-lab.org 