Fibronectin peptides that bind PDGF-BB enhance survival of cells and tissue under stress

Stressors after injury from a multitude of factors can lead to cell death. We have identified four fibronectin (FN) peptides: two from the first FN type III repeat (FNIII₁), one from the 13th FN type III repeat (FNIII ₁₃), and one from FN variable region (IIICS), which when tethered to a surface acted as platelet-derived growth factor-BB (PDGF-BB) enhancers to promote cell survival. One of the FNIII 1 peptides and its smallest (14-mer) bioactive form (P12) were also active in solution. Specifically, P12 bound PDGF-BB (K_D =200 nM), enhanced adult human dermal fibroblast (AHDF) survival under serum starvation, oxidative or endoplasmic reticulum stressors, and limited burn-injury progression in a rat hot comb model. Furthermore, P12 inhibited endoplasmic reticulum stress-induced c-Jun N-terminal kinase (JNK) activation. Although many growth factors have been found to bind FN directly or indirectly, here we identify peptide sequences of growth factor-binding sites in FN. The finding of these peptides further delineated how the extracellular matrix protein FN can support cell survival. As the peptide P12 is active in either soluble form or tethered to a substrate, it will have multifactorial uses as a bioactive peptide by itself or in tissue engineering.