Highlights
- •Role of TRP channels in wound contracture is elucidated using a reconstruction model.
- •Keratinocyte-derived TGF-β1 secretion and fibroblast differentiation are clarified.
- •TRPV2 inhibitors attenuate TGF-β-mediated contraction of the model.
- •TRPV2 channels are markedly expressed in this model.
- •TRPV2 is a possible promising target to ameliorate scar formation.
Abstract
Background
Keratinocytes release several factors that are involved in wound contracture and scar
formation. We previously reported that a three-dimensional reconstruction model derived
from rat skin represents a good wound healing model.
Objective
We characterized the role of transient receptor potential (TRP) channels in the release
of transforming growth factor (TGF)-β1 from keratinocytes and the differentiation
of fibroblasts to identify possible promising pharmacological approaches to prevent
scar formation and contractures.
Methods
The three-dimensional culture model was made from rat keratinocytes seeded on a collagen
gel in which dermal fibroblasts had been embedded.
Results
Among the TRP channel inhibitors tested, the TRPV2 inhibitors SKF96365 and tranilast
attenuated most potently keratinocyte-dependent and — independent collagen gel contraction
due to TGF-β signaling as well as TGF-β1 release from keratinocytes and α-smooth muscle
actin production in myofibroblasts. Besides the low amounts detected in normal dermis,
TRPV2 mRNA and protein levels were increased after fibroblasts were embedded in the
gel. TRPV2 was also expressed in the epidermis and keratinocyte layers of the model.
Both inhibitors and TRPV2 siRNA attenuated the intracellular increase of Ca2+ induced by the TRPV agonist 2-aminoethoxydiphenyl borate in TGF-β1-pretreated fibroblasts.
Conclusion
This is the first study to show that compounds targeting TRPV2 channels ameliorate
wound contraction through the inhibition of TGF-β1 release and the differentiation
of dermal fibroblasts in a culture model.
Keywords
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Article info
Publication history
Published online: March 06, 2018
Accepted:
March 1,
2018
Received in revised form:
February 27,
2018
Received:
January 9,
2018
Identification
Copyright
© 2018 Published by Elsevier B.V. on behalf of Japanese Society for Investigative Dermatology.
