Matrix proteoglycans as effector molecules for epithelial cell function

Abstract

Matrix proteoglycans are complex molecules composed of a core protein and glycosaminoglycan side chains. Once thought to be the molecular glue providing structural support and imparting biomechanical properties to lung tissue, it is now apparent that proteoglycans are important biological modifiers which regulate processes such as lung development, homeostasis, inflammation and wound healing. The diverse roles of proteoglycans in the extracellular matrix suggest that these molecules play a critical role in normal and diseased lungs. This short article will discuss the role extracellular matrix proteoglycans play in regulating epithelial cell function in the lungs.

Glycosaminoglycan binding motif at S1/S2 proteolytic cleavage site on spike glycoprotein may facilitate novel coronavirus (SARS-CoV-2) host cell entry

“…Based on our discovery of GAG-binding and GAGbinding-like motifs at site 1 (within the RBD, Y453-S459), site 2 (at the proteolytic cleavage site at S1/S2 junction, P681-S686), and site 3 (at the S2' proteolytic cleavage site, S810-S816), we hypothesized that SARS-CoV-2 may also interact with host cell surface GAGs through its SGPs to invade host cell (Fig 1, S2 Fig, S3 Fig). The predominant GAG in normal human lung is HS followed by CS [22] and it is noteworthy that lung tissue is rich in mast cells and has been a source of commercial HP [23]. Using unbiased docking, we found that TriS HS hexasaccharide 5D).…”

Increased deposition of chondroitin/dermatan sulfate glycosaminoglycan and upregulation of β1,3-glucuronosyltransferase I in pulmonary fibrosis

“…PGs are key components of the ECM of the lung (35) and are characterized by the presence of one or multiple glycosaminoglycan (GAG) side chains covalently linked to a core protein. PGs provide the tissue with many of its characteristic physicochemical properties and control cellular activity (7,15). Evidence to date suggests that many of these biological interactions are properties of the GAG side chains, which play important roles in growth factor signaling, cellular differentiation, morphogenesis, and pathophysiology (17, 19, 21, 28, 36 -38, 41).…”

Anatomy of the Lungs

“…A growing view is emerging of the lung's extracellular matrix components as regulators of lung physiology, helping in determining epithelial cell phenotype; binding of and subsequent signaling by cytokines, chemokines, and growth factors; and mediating cell proliferation, migration, differentiation, and apoptosis. [16][17][18][19][20][21][22][23] In disease states, degradation products of extracellular matrix components may activate the Toll-like receptor pathways (see later discussion); thus the degradation products may serve as endogenous 18,[22][23][24] Within this gel-like interstitium reside several varieties of interstitial cells (contractile and noncontractile interstitial cells, 25,26 mast cells, plasma cells, and occasional leukocytes). The remainder of the interstitium is The anatomic dead space, as measured by the singlebreath nitrogen dilution technique, is approximately 30% of each tidal volume.…”