Helmholtz Munich

Collagen biosynthesis and maturation in lung fibrosis

Our work aims at unravelling the contributions of the extracellular matrix (ECM) on the regulation of dynamic cell circuits, on environmental barrier immunity and on immunometabolic programming.

Our work aims at unravelling the contributions of the extracellular matrix (ECM) on the regulation of dynamic cell circuits, on environmental barrier immunity and on immunometabolic programming..

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The extracellular matrix (ECM) is a ubiquitous complex glycoprotein network, which provides a scaffold for cellular support and migration and a mechanical barrier in all tissue types and compartments including the lung. In addition, the ECM governs cell behavior and function by virtue of distinct biomechanical and molecular cues. Its components as well as ECM-modifying factors are secreted by multiple cell types including lung epithelial cells, lung fibroblasts, and immune cells. Hence, the ECM underlies constant remodeling and is drastically changed in chronic lung disease.

Picture: Nuclei (blue) and secreted extracellular matrix deposits (red)

Collagen is the main ECM component in virtually all tissues. There are at least 28 different collagen types, which are sub-classified in seven categories, based on their heterogeneous supramolecular structures. In addition, collagen chains are heavily modified by an intracellular protein machinery prior to secretion, as well as further processed, modified, and cross-linked by enzymatic and non-enzymatic events in the extracellular space. Given the high abundance of collagen and the drastic changes in disease, it is of critical importance to decipher how changes in collagen composition and post-translational modification (PTM) patterns affect adhesion, migration and function of cells in normal physiology, in the context of environmental injury, and in lung disease.

Picture: Immunofluorescent staining of a normal human lung section for type IV collagen (green)