TRPML1 suppresses pulmonary fibrosis by limiting collagen and elastin deposition

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 a

SUBMITTER: Eva-Maria Weiden 

PROVIDER: S-SCDT-10_1038-S44318-026-00712-4 | biostudies-other |

REPOSITORIES: biostudies-other