Collagen Type I as a Ligand for Receptor-Mediated Signaling

Abstract

Collagens form the fibrous component of the extracellular matrix in all multi-cellular animals. Collagen type I is the most abundant collagen present in skin, tendons, vasculature, as well as the organic portion of the calcified tissue of bone and teeth. This review focuses on numerous receptors for which collagen acts as a ligand, including integrins, discoidin domain receptors DDR1 and 2, OSCAR, GPVI, G6b-B, and LAIR-1 of the leukocyte receptor complex (LRC) and mannose family receptor uPARAP/Endo180. We explore the process of collagen production and self-assembly, as well as its degradation by collagenases and gelatinases in order to predict potential temporal and spatial sites of action of different collagen receptors. While the interactions of the mature collagen matrix with integrins and DDR are well-appreciated, potential signals from immature matrix as well as collagen degradation products are possible but not yet described. The role of multiple collagen receptors in physiological processes and their contribution to pathophysiology of diseases affecting collagen homeostasis require further studies.

Tendon‐derived extracellular matrix induces mesenchymal stem cell tenogenesis via an integrin/transforming growth factor‐β crosstalk‐mediated mechanism

“…Notwithstanding this limitation, our findings still demonstrate the importance of RGD binding‐mediated fibronectin matrix scaffold assembly, which is essential for assembly of collagen and other ECM matrix components 52,53 . To understand tECM bioactivity further, it will be important to elucidate the interactions among other tendon ECM molecules (eg, laminin, vitronectin, tenascin) and their integrins or non‐integrin receptors (eg, receptor tyrosine kinases, leukocyte receptor complex, or uPARAP/Endo180) 54 …”

Extracellular Matrix‐Based Strategies for Immunomodulatory Biomaterials Engineering

“…Collagens used most often in biomaterials applications, Types I–III, V, and XI have fibrillar quaternary structures. Immune cells express a number of receptors that bind directly to collagen, including integrins, discoidin domain receptors DDR1 and 2, and leukocyte‐associated immunoglobulin‐like receptor‐1 (LAIR‐1) of the leukocyte receptor complex . Collagens I–III and XVII are high‐affinity ligands for LAIR‐1 receptors on immune cells, where binding prevents degranulation of peripheral basophils, and more generally suppressed immune cell activity .…”

Collagen Density Modulates the Immunosuppressive Functions of Tumor-Associated Macrophages

“…Another possibility is that the increased number of binding sites for collagen receptors found in the high density collagen matrices could potentiate collagen-induced signaling. In this regard, it could be interesting to investigate the role of different collagen receptors, including β1integrins, discoidin domain receptor tyrosine kinase 1 (DDR1), DDR2, osteoclast-associated receptor (OSCAR), leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1), and mannose receptor (MR) 56,57 . It also remains to be elucidated which intracellular signaling pathways are responsible for the collagen-induced modulation of macrophages.…”