Extracellular matrix in skin diseases: The road to new therapies

Background: The extracellular matrix (ECM) is a vital structure with a dynamic and complex organization
that plays an essential role in tissue homeostasis. In the skin, the ECM is arranged into two types of com-
partments: interstitial dermal matrix and basement membrane (BM). All evidence in the literature sup-
ports the notion that direct dysregulation of the composition, abundance or structure of one of these
types of ECM, or indirect modifications in proteins that interact with them is linked to a wide range of
human skin pathologies, including hereditary, autoimmune, and neoplastic diseases. Even though the
ECM’s key role in these pathologies has been widely documented, its potential as a therapeutic target
has been overlooked.
Aim of review: This review discusses the molecular mechanisms involved in three groups of skin ECM-
related diseases - genetic, autoimmune, and neoplastic – and the recent therapeutic progress and oppor-
tunities targeting ECM.
Key scientific concepts of review: This article describes the implications of alterations in ECM components
and in BM-associated molecules that are determinant for guaranteeing its function in different skin dis-
orders. Also, ongoing clinical trials on ECM-targeted therapies are discussed together with future oppor-
tunities that may open new avenues for treating ECM-associated skin diseases.