Fragile scaffolding modifies lung infrastructure

Our lungs work tirelessly throughout the day to keep us breathing, dilating and contracting in a transparent way. When the lung tissue is damaged and marked, it can lose flexibility, making it harder to breathe.

Pulmonary scars can lead to diseases such as pulmonary fibrosis and life-threatening complications. Pulmonary fibrosis can also develop in patients with a rare hereditary disorder called Hermansky-Pudlak syndrome. Researchers at Freddy Romero's lab at the Center for Translational Medicine at Thomas Jefferson University are trying to understand what contributes to the development of pulmonary fibrosis in animal models and patients with Hermansky syndrome. Pudlak.

The cells of all the tissues of our body are held together by a scaffold called extracellular matrix. When this scaffold holding the fabric in place is damaged, the structural integrity of the fabric also changes. Enzymes called matrix metalloproteinases (MMPs) usually help to eliminate scaffolds that are no longer needed, but these enzymes can become hyperactive in case of disease. MMPs are often modified in many lung diseases, where a more fragile scaffold can cause stiffness and inflammation of the surrounding tissues. However, it is not known what role these enzymes play in Hermansky-Pudlak syndrome.

In this study, the researchers examined whether the activity of MMPs was impaired in pulmonary tissues affected by Hermansky-Pudlak syndrome and how these changes were related to the onset of pulmonary fibrosis. The results were published in Orphanet Journal of Rare Diseases The 4th of July.

They found that certain subsets of MMPs were elevated in the lungs of murine models of the disease, as well as in fluid from the lungs of patients with Hermansky-Pudlak syndrome. In mouse models and patient samples, MMP was detectable at high levels prior to the development of fibrosis, indicating that high levels of MMP may be badociated with the onset of the disease rather than the disease. 39, to its evolution.

Previously, it was unclear how mutations underlying Hermansky-Pudlak syndrome could lead to the development of pulmonary fibrosis. This study provides a new link that could be useful in the diagnosis and treatment of the disease. The first author of the article, Ross Summer, MD of the Jane & Leonard Korman Respiratory Institute, explains: "Our work supports the idea that dysregulation of MMPs contributes to the development of pulmonary fibrosis. suggests that unique modifications be exploited for the diagnosis and / or prognosis of a pulmonary disease related to the Hermansky-Pudlak syndrome. "