The PHSRN sequence induces extracellular matrix invasion and accelerates wound healing in obese diabetic mice
Donna L. Livant, … , Stephen P. Ethier, Sonja Markwart
Donna L. Livant, … , Stephen P. Ethier, Sonja Markwart
Published June 1, 2000
Citation Information: J Clin Invest. 2000;105(11):1537-1545. https://doi.org/10.1172/JCI8527.
View: Text | PDF
Article

The PHSRN sequence induces extracellular matrix invasion and accelerates wound healing in obese diabetic mice

Abstract

The PHSRN sequence of the plasma fibronectin (pFn) cell-binding domain induces human keratinocytes and fibroblasts to invade the naturally serum-free extracellular matricies of sea urchin embryos. The potency of acetylated, amidated PHSRN (Ac-PHSRN-NH2) is significantly increased, making it more active on a molar basis than the 120-kDa cell-binding domain of pFn. Arginine is important to this activity because PHSAN and PHSEN are inactive, as is a randomized sequence peptide, Ac-HSPNR-NH2. One treatment with Ac-PHSRN-NH2 stimulates reepithelialization and contraction of dermal wounds in healing-impaired, obese diabetic C57BL6/KsJ db/db mice. Wound closure is equally rapid in treated db/db and db/+ mice and may be more rapid than in untreated nondiabetic db/+ littermates. In contrast, treatment with either Ac-HSPNR-NH2 or normal saline (NS) has no effect. Analysis of sectioned db/db wounds shows that, in contrast to treatment with Ac-HSPNR-NH2 or NS, a single Ac-PHSRN-NH2 treatment stimulates keratinocyte and fibroblast migration into wounds, enhances fibroplasia and vascularization in the provisional matrix, and stimulates the formation of prominent fibers that may be associated with wound contraction.

Authors

Donna L. Livant, R. Kaye Brabec, Kotoku Kurachi, David L. Allen, Yanling Wu, Ronald Haaseth, Philip Andrews, Stephen P. Ethier, Sonja Markwart

×

Figure 8

Options: View larger image (or click on image) Download as PowerPoint
Effect of Ac-PHSRN-NH2, Ac-HSPNR-NH2, or NS alone on the presence of fib...
Effect of Ac-PHSRN-NH2, Ac-HSPNR-NH2, or NS alone on the presence of fibroblasts in the provisional matrix of db/db dermal wounds 3 days after wounding. (a) A section of an Ac-PHSRN-NH2–treated wound in a db/db mouse 3 days after wounding, Bar, 20 μm. (b) A section of an Ac-PHSRN-NH2–treated wound in a db/db mouse 3 days after wounding. Bar, 20 μm. (c) A section of an NS-treated wound in a db/db mouse 3 days after wounding, Bar, 20 μm. (d) A section of an Ac-HSPNR-NH2–treated wound in a db/db mouse 3 days after wounding. Bar, 20 μm. a–d, × 400.