Dermatan Sulfate Released after Injury Is a Potent Promoter of Fibroblast Growth Factor-2 Function

Abstract

Proteoglycans have been shown in vitro to bind multiple components of the cellular microenvironment that function during wound healing. To study the composition and function of these molecules when derived from an in vivo source, soluble proteoglycans released into human wound fluid were characterized and evaluated for influence on fibroblast growth factor-2 activity. Immunoblot analysis of wound fluid revealed the presence of syndecan-1, syndecan-4, glypican, decorin, perlecan, and versican. Sulfated glycosaminoglycan concentrations ranged from 15 to 65 g/ml, and treatment with chondroitinase B showed that a large proportion of the glycosaminoglycan was dermatan sulfate. The total glycosaminoglycan mixture present in wound fluid supported the ability of fibroblast growth factor-2 to signal cell proliferation. Dermatan sulfate, and not heparan sulfate, was the major contributor to this activity, and dermatan sulfate bound FGF-2 with K d ‫؍‬ 2.48 M. These data demonstrate that proteoglycans released during wound repair are functionally active and provide the first evidence that dermatan sulfate is a potent mediator of fibroblast growth factor-2 responsiveness.

FGF-2 regulation of neurogenesis in adult hippocampus after brain injury

“…Normally FGF-2 does not have a signal sequence for cell secretion through the Golgi apparatus (34)(35)(36)(37), and it is probably released extracellularly only after cell damage. According to this hypothesis, it is speculated that FGF-2 plays a negligible role in the normal state, but with increasing damage, more FGF-2 is released and stimulates neurogenesis.…”

“…Regarding FGF-2 release from cells, plasminogen activatormediated proteolysis provides a mechanism for the dissociation of biologically active FGF-2-heparan sulfate complexes from the extracellular matrix (34)(35)(36)(37). Recently, cerebral ischemia and kainate seizures were shown to activate plasminogen activator (42)(43)(44)(45)(46).…”

Structural and Functional Characterization of Oversulfated Chondroitin Sulfate/Dermatan Sulfate Hybrid Chains from the Notochord of Hagfish

“…The binding of growth factors (including FGF-2) to HS and DS requires IdoUA residues (43,44). However, CS-E exclusive of IdoUA also exhibits specific interactions of high affinity with various heparin-binding growth factors (13), implying the importance of the E unit and the sulfation patterns as well.…”

“…Interestingly, such VEGF types bind to cell-surface and extracellular matrix-associated HS-PGs, releasing angiogenic factors such as FGF-2, which are stored on the heparin-like molecules in the extracellular matrix (54). Notably, DS released after injury is a potent promoter of FGF-2 activity (43). The sensorgrams obtained in this study for the binding of FGF-2, FGF-16, HB-EGF, and VEGF 165 to CS-H were similar to each other, showing a faster association and dissociation compared with the other four growth factors tested (Fig.…”

Analysis of the structure and neuritogenic activity of chondroitin sulfate/dermatan sulfate hybrid chains from porcine fetal membranes

“…The in situ tissue-engineered esophagus, which is prepared by cultivating oral keratinocytes and fibroblasts on human AM, can successfully replace the intrathoracic esophagus [37]. Since CS/DS is involved in biological events such as cell proliferation [3,6], viral infection [46], inflammation [47], anti-coagulation [33], and wound healing [5,6,48], it may contribute to some of the biological activities of AM described above. The information obtained in this study facilitates deeper understanding of the biological activities of AM, and suggests potential applications of FM-CS/DS chains.…”