The PHSRN sequence induces extracellular matrix invasion and accelerates wound healing in obese diabetic mice.
The PHSRN sequence of the plasma fibronectin (pFn) cell-binding domain induces human keratinocytes and fibroblasts to invade the naturally serum-free extracellular matrices of sea urchin embryos. The potency of acetylated, amidated PHSRN (Ac-PHSRN-NH(2)) 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-NH(2). One treatment with Ac-PHSRN-NH(2) 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-NH(2) or normal saline (NS) has no effect. Analysis of sectioned db/db wounds shows that, in contrast to treatment with Ac-HSPNR-NH(2) or NS, a single Ac-PHSRN-NH(2) 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.
Livant
D L
DL
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0616, USA. dlivant@umich.edu
Brabec
R K
RK
Kurachi
K
K
Allen
D L
DL
Wu
Y
Y
Haaseth
R
R
Andrews
P
P
Ethier
S P
SP
Markwart
S
S
D000818:Animals; D001665:Binding Sites; D002465:Cell Movement; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000494:pharmacology*; D003920:Diabetes Mellitus / Q000503:physiopathology*; D005109:Extracellular Matrix / Q000187:drug effects*; D005347:Fibroblasts / Q000502:physiology; D005353:Fibronectins / Q000494:pharmacology*; D015603:Keratinocytes / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D010446:Peptide Fragments / Q000494:pharmacology*; D017469:Receptors, Fibronectin / Q000502:physiology; D014945:Wound Healing / Q000187:drug effects*
D002630:Chemotactic Factors; D005353:Fibronectins; D010446:Peptide Fragments; D017469:Receptors, Fibronectin