Fibroblast Migration on Fibronectin Requires Three Distinct Functional Domains

Abstract

Mesenchymal cell movement is normally constrained; however, fibronectin can provide a pathway for stromal cell migration during embryogenesis, morphogenesis, and wound healing. Cells can adhere to fibronectin via integrin and nonintegrin receptors, which bind multiple unique peptide sequences. Synthetic peptides and recombinant proteins were used to delineate the functional domains needed for human fibroblast migration over fibronectin. The 9th and 10th fibronectin type III repeats, which contain RGD and PHSRN synergy cell attachment sequences, support almost maximal fibroblast attachment, but not migration of primary dermal fibroblasts. Specific sequences within the heparin domain and the IIICS region are also required for migration. These findings predict and additional data confirm the necessity for the cooperation of multiple integrin and nonintegrin receptors for fibroblast migration on fibronectin. Such stringency of migration most likely imposes an immense constraint on normal mesenchymal cell mobility in unperturbed tissue. Loss of such restraint may be critical for the migration cancer cells through the extracellular matrix.

Sphingosine 1-Phosphate Potentiates Human Lung Fibroblast Chemotaxis through the S1P2 Receptor

“…Many cells migrate directionally in response to a variety of extracellular signals, including gradients of chemokines, growth factors, or extracellular matrix molecules such as fibronectin, a potent chemoattractant for fibroblasts. In this context, the migration of fibroblasts from neighboring connective tissue into sites of inflammation is essential for tissue repair and wound healing (3,4). Sphingosine 1-phosphate (S1P) is a sphingolipid metabolite that has a variety of biological effects on cells, including modulation of proliferation, differentiation, cytoskeleton organization, motility, apoptosis, neurite retraction, contraction, angiogenesis, and platelet activation (5)(6)(7)(8).…”

“…S1P is produced by various cell types, including platelets, in response to diverse stimuli. S1P functions as a specific ligand for a family of G protein-coupled receptors (GPCRs) named S1P 1 , S1P 2 , S1P 3 , S1P 4 , and S1P 5 (previously termed Edg 1,5,3,6, and 8, respectively) (9). The majority of the biological functions of S1P are mediated through these receptors (10); however, considerable evidence also indicates that S1P can act as an intracellular second messenger (11).…”

Electrospray deposition in vacuum as method to create functionally active protein immobilization on polymeric substrates

“…This behaviour is related to the ability of fibronectin to change its native conformation when absorbed on the substrate, influencing the cell adhesion and spreading [35]. The role of the RGD sequence within fibronectin in fibroblast adhesion and migration is well known [36], and it is reasonable to propose that the presence of a higher fibronectin deposition can increase the chance to find more RGD complexes on the surface favouring cell adhesion at that location. It should be noted, however, that cellular attachment to fibronectin can occur through a variety of mechanisms, involving integrins, syndecans, and other receptor systems.…”

Migratory potential of rheumatoid arthritis synovial fibroblasts: Additional perspectives

“…[1][2][3][4][5] Rheumatoid arthritis (RA) synovial fibroblasts (SFs) have the ability to physiologically remodel mesenchymal structures. 1,[6][7][8] This ability has also been demonstrated in wound healing, [1][2][3][4][5][9][10][11] which includes a temporary change from the "resting" to the "activated" phenotype of the fibroblast 3 leading to the ability to migrate short distances since fibroblasts are normally regarded as resident cells. [1][2][3] Under pathophysiological conditions different local cells can acquire the potential for long distance migration.…”

“…The pathophysiology of RA involves different cell-types. 5,6,17,27,[31][32][33][34][35][36] Activated RASFs, which are present in large numbers in rheumatoid synovium, are one of the key players in the matrix destructive process of RA. 1 Of the various pathogenic subcutaneously at the contralateral site of the animal.…”