肺線維症におけるイオンチャネルの組織リモデリング制御機構を解明(Pulmonary fibrosis: ion channel regulates tissue remodeling)

2026-02-19 ミュンヘン大学(LMU)

<関連情報>

• https://www.lmu.de/en/newsroom/news-overview/news/pulmonary-fibrosis-ion-channel-regulates-tissue-remodeling-c2668205.html
• https://link.springer.com/article/10.1038/s44318-026-00712-4

TRPML1はコラーゲンとエラスチンの沈着を制限することで肺線維症を抑制する TRPML1 suppresses pulmonary fibrosis by limiting collagen and elastin deposition

Eva-Maria Weiden,Zala Serianz,Yvonne Klingl,Simone Jörs,Dawid Jaślan,Marco Keller,Sandra Prat Castro,Mane Mkhitaryan,Aicha Jeridi,Daria Briukhovetska,Barbara Spix,Anna Scotto Rosato,Ahmed Agami,Herbert B Schiller,Suhasini Rajan,Johann Schredelseker,Giorgio Fois,Manfred Frick,Sebastian Kobold,Margarethe Klein,Fabian Geisler,Jorge Garcia-Fortanet,Leon O Murphy,Franz Bracher,… Christian Grimm
The EMBO Journal  Published:19 February 2026
DOI:https://doi.org/10.1038/s44318-026-00712-4

Abstract

In pulmonary fibrosis lung tissue is thickened and scarred, and the lungs become progressively stiffer and smaller, leading to low levels of blood oxygen and shortness of breath. Lung fibrosis is not curable and life expectancy is reduced. Fibrosis is characterized by an increased accumulation of extracellular matrix (ECM) proteins such as collagen and elastin. ECM proteins are degraded predominantly by matrix metalloproteinases (MMPs). Here, we show that the lysosomal cation channel TRPML1, which causes the lysosomal storage disorder mucolipidosis type IV (MLIV) when mutated or lost, regulates the levels of MMPs in the ECM of mouse airways, modulating exocytosis of MMP2, 8, 9, 12, and 19, which mediate collagen/elastin degradation. While TRPML1 loss reduces MMP levels in lung macrophage and fibroblast supernatants, small molecule activation of TRPML1 results in increased levels. MLIV mice display a fibrosis-like lung phenotype similar to the phenotype evoked by bleomycin. We thus identify TRPML1 as a regulator of MMP release in the lung with loss of TRPML1 resulting in lung fibrosis due to excessive extracellular collagen and elastin accumulation.