TAT-Mediated Acidic Fibroblast Growth Factor Delivery to the Dermis Improves Wound Healing of Deep Skin Tissue in Rat.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
Our results demonstrate that TAT-aFGF has a favorable therapeutic effect on the healing of subcutaneous deep tissue injury.
School of Pharmacy, Wenzhou Medical University, Chashan University Park, Wenzhou 325035, China.
Long
L
Zheng
School of Pharmacy, Wenzhou Medical University, Chashan University Park, Wenzhou 325035, China.
Qi
Q
Hui
School of Pharmacy, Wenzhou Medical University, Chashan University Park, Wenzhou 325035, China.
Lu
L
Tang
School of Pharmacy, Wenzhou Medical University, Chashan University Park, Wenzhou 325035, China.
Lulu
L
Zheng
School of Pharmacy, Wenzhou Medical University, Chashan University Park, Wenzhou 325035, China.
Zi
Z
Jin
School of Pharmacy, Wenzhou Medical University, Chashan University Park, Wenzhou 325035, China.
Bingjie
B
Yu
School of Pharmacy, Wenzhou Medical University, Chashan University Park, Wenzhou 325035, China.
Zhitao
Z
Wang
School of Pharmacy, Wenzhou Medical University, Chashan University Park, Wenzhou 325035, China.
Peng
P
Lin
School of Pharmacy, Wenzhou Medical University, Chashan University Park, Wenzhou 325035, China.
Weidan
W
Yu
School of Pharmacy, Wenzhou Medical University, Chashan University Park, Wenzhou 325035, China; Ministry of Education Engineering Research Center of Bioreactor and Pharmaceutical Development, Jilin Agricultural University, Changchun, 130118, China.
Haiyan
H
Li
School of Pharmacy, Wenzhou Medical University, Chashan University Park, Wenzhou 325035, China; Ministry of Education Engineering Research Center of Bioreactor and Pharmaceutical Development, Jilin Agricultural University, Changchun, 130118, China.
Xiaokun
X
Li
School of Pharmacy, Wenzhou Medical University, Chashan University Park, Wenzhou 325035, China; Ministry of Education Engineering Research Center of Bioreactor and Pharmaceutical Development, Jilin Agricultural University, Changchun, 130118, China.
Xiaojie
X
Wang
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D053938:DNA Fragmentation; D020405:Dermis / Q000378:metabolism*; D016220:Fibroblast Growth Factor 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D017207:Rats, Sprague-Dawley; D014945:Wound Healing / Q000502:physiology*
D016220:Fibroblast Growth Factor 1