TAT-Mediated Acidic Fibroblast Growth Factor Delivery to the Dermis Improves Wound Healing of Deep Skin Tissue in Rat
Open Access
- 13 August 2015
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 10 (8), e0135291
- https://doi.org/10.1371/journal.pone.0135291
Abstract
The definition of deep tissue injury was derived from multiple clinical cases as “A purple or maroon localized area of discolored intact skin or blood-filled blister due to damage of underlying soft tissue from pressure and/or shear”. Acidic fibroblast growth factor (aFGF) significantly improves wound healing under diabetic conditions. However, to date, the therapeutic application of aFGF has been limited, due to its low delivery efficiency and short half-life. Using an animal model of magnet-induced pressure ulcers, transactivator of transcription protein (TAT)-aFGF was evaluated for transdermal delivery and wound healing. Immunohistochemistry and Western blotting were also performed to determine the expression of transforming growth factor (TGF)-β1, α-smooth muscle actin (α-SMA), CD68, proliferating cell nuclear antigen (PCNA) and TGF-β-receptor II (TGF- βRII) in cultured human dermal fibroblasts. We found that that mice treated with TAT-aFGF had higher accumulation of aFGF in both dermis and subcutaneous tissues compared with mice treated with aFGF alone. In the remodeling phase, TAT-aFGF treatment decreased the expression of α-SMA to normal levels, thereby facilitating normal wound healing processes and abrogating hypertrophic scarring. In human dermal fibroblasts, TAT-aFGF reversed the suppressive effect of TNF-α on α-SMA expression and restored TGF-βRII and TGF-β1 expression. Our results demonstrate that TAT-aFGF has a favorable therapeutic effect on the healing of subcutaneous deep tissue injury.This publication has 35 references indexed in Scilit:
- Distinct fibroblast lineages determine dermal architecture in skin development and repairNature, 2013
- Acceleration of diabetic‐wound healing with PEGylated rhaFGF in healing‐impaired streptozocin diabetic ratsWound Repair and Regeneration, 2011
- Improved refractory wound healing with administration of acidic fibroblast growth factor in diabetic ratsDiabetes Research and Clinical Practice, 2011
- Update on Pressure Ulcer Management and Deep Tissue InjuryAnnals of Pharmacotherapy, 2010
- Controlled delivery of heat shock protein using an injectable microsphere/hydrogel combination system for the treatment of myocardial infarctionJournal of Controlled Release, 2009
- The FGF family: biology, pathophysiology and therapyNature Reviews Drug Discovery, 2009
- Randomized, multicenter, double‐blind, and placebo‐controlled trial using topical recombinant human acidic fibroblast growth factor for deep partial‐thickness burns and skin graft donor siteWound Repair and Regeneration, 2007
- National Pressure Ulcer Advisory Panel's Updated Pressure Ulcer Staging SystemAdvances in Skin & Wound Care, 2007
- Pressure-Related Deep Tissue Injury under Intact Skin and the Current Pressure Ulcer Staging SystemsAdvances in Skin & Wound Care, 2005
- Acidic Fibroblast Growth Factor: Evaluation of Topical Formulations in a Diabetic Mouse Wound Healing ModelPharmaceutical Research, 1994