If this breakdown does not occur, collagen and elastin accumulate in the lung tissue. This results in structural and functional changes that closely resemble the clinical picture of pulmonary fibrosis. The study thus opens up a new molecular starting point for anti-fibrotic therapies - a field with considerable medical need. The results were published in the EMBO Journal.

The functional effects of the missing channel were clear: the lungs of the knockout mice showed increased stiffness and reduced distensibility, while histological staining revealed increased deposition of collagen and elastin in the lung tissue.

It is noteworthy that the observed phenotype corresponds in many parameters to the established bleomycin model of pulmonary fibrosis, in which administration of the cytostatic agent bleomycin leads to inflammation-triggered fibrotic scarring of the lung. Additional bleomycin treatment did not further worsen the condition of the TRPML1-deficient animals in the current experiment. Apparently, the fibrotic process was already at its maximum.

"The changes we see are functionally and histologically almost indistinguishable from the classic experimental fibrosis model," says Grimm. "This underlines the central role of TRPML1 in lung tissue remodeling."

In experiments, the team showed that the targeted pharmacological activation of TRPML1 significantly increases the release of the affected matrix metalloproteinases, but only in cells with an intact channel and not in cells that lack this channel.

In addition, the researchers point to another important finding: mutations in the TRPML1 gene cause the rare lysosomal storage disease mucolipidosis type IV (MLIV). The current results indicate that patients may carry a previously underestimated risk of fibrotic changes in the lungs. "Our findings not only open up new perspectives for the treatment of pulmonary fibrosis, but also shed new light on the systemic effects of lysosomal diseases," says Grimm.