The Extracellular Matrix Across States: From Homeostasis to Dysfunction in Rare Connective Tissue Disorders

The extracellular matrix (ECM) provides a dynamic environment in which the fine balance between biosynthesis, degradation and/or maturation of matrix components critically governs its structure and function. It is well established that the ECM plays a central role not only in the physiological functions of tissues, but also in the pathogenesis and the progression of several human diseases, ranging from cancer, fibrosis to genetic diseases. In this perspective, we will focus on the Ehlers‐Danlos Syndromes (EDS), an umbrella term for a clinically and genetically heterogeneous group of connective tissue disorders and investigate the link between matrix alterations and typical clinical features of the disease. After discussing the various models used to explore the complexity of ECM network, we aim at illustrating the need of multidisciplinary approaches to gain insight into the disease and the underlying molecular mechanisms in order to propose new therapeutic strategies to improve patient care and management.