Matricellular proteins in drug delivery: Therapeutic targets, active agents, and therapeutic localization

Abstract

Extracellular matrix is composed by a complex array of molecules that together provide structural and functional support to cells. These properties are mainly mediated by the activity of collagenous and elastic fibers, proteoglycans, and proteins such as fibronectin and laminin. ECM composition is tissue-specific and could include matricellular proteins whose primary role is to modulate cell-matrix interactions. In adults, matricellular proteins are primarily expressed during injury, inflammation and disease. Particularly, they are closely associated with the progression and prognosis of cardiovascular and fibrotic diseases, and cancer. This review aims to provide an overview of the potential use of matricellular proteins in drug delivery including the generation of therapeutic agents based on the properties and structures of these proteins as well as their utility as biomarkers for specific diseases.

MicroRNAs associated with lung squamous cell carcinoma: New prognostic biomarkers and therapeutic targets

“…For example, cadherin‐11 affects the activity levels of crac1 and STAT 3, which in turn regulates the P53 signaling pathway . Proteoglycans have an indispensable role in the tumor microenvironment, and as a result, many studies have described their potential use as target genes, biomarkers, and active agents . Moreover, it has been found that mutations in cell cycle genes can affect the differentiation of squamous cells in the course of modern anticancer treatment research .…”

Extracellular matrix hyaluronan signals via its CD44 receptor in the increased responsiveness to mechanical stimulation

“…There is increasing evidence stressing the important role of the ECM in the regulation/modulation of the inflammatory process (Toole, 2004; De Bock et al, 2015; Murai, 2015; Schwertfeger et al, 2015; Sawyer and Kyriakides, 2016). For example, versican, hyaluronan and other components of the ECM such as fibronectin or laminin, have been shown to interact with resident cells during inflammation, contributing to their proliferation and migration (Gee et al, 2004; Petrey and de la Motte, 2014; Andersson-Sjöland et al, 2015; Schwertfeger et al, 2015).…”

The extracellular matrix in myocardial injury, repair, and remodeling

“…Distinct actions of matricellular protein fragments further complicate therapeutic implementation. Identification of the functional domains responsible for specific protective or detrimental matricellular actions is needed in order to design peptide-based strategies that simulate these effects (12,135).…”