A fragment of secreted Hsp90α carries properties that enable it to accelerate effectively both acute and diabetic wound healing in mice.
Wounds that fail to heal in a timely manner, for example, diabetic foot ulcers, pose a health, economic, and social problem worldwide. For decades, conventional wisdom has pointed to growth factors as the main driving force of wound healing; thus, growth factors have become the center of therapeutic developments. To date, becaplermin (recombinant human PDGF-BB) is the only US FDA-approved growth factor therapy, and it shows modest efficacy, is costly, and has the potential to cause cancer in patients. Other molecules that drive wound healing have therefore been sought. In this context, it has been noticed that wounds do not heal without the participation of secreted Hsp90α. Here, we report that a 115-aa fragment of secreted Hsp90α (F-5) acts as an unconventional wound healing agent in mice. Topical application of F-5 peptide promoted acute and diabetic wound closure in mice far more effectively than did PDGF-BB. The stronger effect of F-5 was due to 3 properties not held by conventional growth factors: its ability to recruit both epidermal and dermal cells; the fact that its ability to promote dermal cell migration was not inhibited by TGF-β; and its ability to override the inhibitory effects of hyperglycemia on cell migration in diabetes. The discovery of F-5 challenges the long-standing paradigm of wound healing factors and reveals a potentially more effective and safer agent for healing acute and diabetic wounds.
Department of Dermatology and Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, California, USA.
Chieh-Fang
CF
Cheng
Divya
D
Sahu
Fred
F
Tsen
Zhengwei
Z
Zhao
Jianhua
J
Fan
Rosie
R
Kim
Xinyi
X
Wang
Kathryn
K
O'Brien
Yong
Y
Li
Yuting
Y
Kuang
Mei
M
Chen
David T
DT
Woodley
Wei
W
Li
D000287:Administration, Topical; D000818:Animals; D000077214:Becaplermin; D002478:Cells, Cultured; D048909:Diabetes Complications / Q000188:drug therapy / Q000503:physiopathology; D018841:HSP90 Heat-Shock Proteins / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D051379:Mice; D008812:Mice, Hairless; D008819:Mice, Nude; D008954:Models, Biological; D010446:Peptide Fragments / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
D018841:HSP90 Heat-Shock Proteins; C533585:HSP90AA2P protein, human; D010446:Peptide Fragments; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D000077214:Becaplermin