scholarly journals Correction: Fibromodulin-Deficiency Alters Temporospatial Expression Patterns of Transforming Growth Factor-β Ligands and Receptors during Adult Mouse Skin Wound Healing

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0246557
Author(s):  
2012 ◽  
Vol 302 (8) ◽  
pp. C1213-C1225 ◽  
Author(s):  
Chen Zhang ◽  
Chek Kun Tan ◽  
Craig McFarlane ◽  
Mridula Sharma ◽  
Nguan Soon Tan ◽  
...  

Myostatin (Mstn) is a secreted growth and differentiation factor that belongs to the transforming growth factor-β (TGF-β) superfamily. Mstn has been well characterized as a regulator of myogenesis and has been shown to play a critical role in postnatal muscle regeneration. Herein, we report for the first time that Mstn is expressed in both epidermis and dermis of murine and human skin and that Mstn-null mice exhibited delayed skin wound healing attributable to a combination of effects resulting from delayed epidermal reepithelialization and dermal contraction. In epidermis, reduced keratinocyte migration and protracted keratinocyte proliferation were observed, which subsequently led to delayed recovery of epidermal thickness and slower reepithelialization. Furthermore, primary keratinocytes derived from Mstn-null mice displayed reduced migration capacity and increased proliferation rate as assessed through in vitro migration and adhesion assays, as well as bromodeoxyuridine incorporation and Western blot analysis. Moreover, in dermis, both fibroblast-to-myofibroblast transformation and collagen deposition were concomitantly reduced, resulting in a delayed dermal wound contraction. These decreases are due to the inhibition of TGF-β signaling. In agreement, the expression of decorin, a naturally occurring TGF-β suppressor, was elevated in Mstn-null mice; moreover, topical treatment with TGF-β1 protein rescued the impaired skin wound healing observed in Mstn-null mice. These observations highlight the interplay between TGF-β and Mstn signaling pathways, specifically through Mstn regulation of decorin levels during the skin wound healing process. Thus we propose that Mstn agonists might be beneficial for skin wound repair.


2021 ◽  
Author(s):  
Jagadeeshaprasad Mashanipalya ◽  
Prem Kumar Govindappa ◽  
Amanda Nelson ◽  
Mark Noble ◽  
John Elfar

Abstract The discovery of ways to enhance skin healing is of great importance due to the frequency and severity of skin wounds. We discovered that 4-aminopyridine (4-AP), a potassium channel blocker, greatly enhances skin wound healing. Benefits include faster wound closure, restoration of normal-appearing skin architecture and epidermal thickness, increased vascularization and increases in K14+ keratinocytes. Hair follicle number was increased, both histologically and by analysis of K15 and K17 expression. Levels of vimentin (which marks fibroblasts) and α-smooth muscle actin (α-SMA, which marks collagen-producing myofibroblasts) increased, as did α-SMA+ cell numbers. 4-AP also increased numbers of axons and S-100+ Schwann cells, and increased expression of p75-NTR and SOX10. Treatment also increased levels of nerve growth factor, transforming growth factor-β, Substance P and PGP9.5, important modulators of wound healing. As 4-AP is already used for treatment of multiple sclerosis and other chronic neurological syndromes, it has strong potential for rapid translational development.


Author(s):  
Min Cheol Kang ◽  
Silvia Yumnam ◽  
Woo Sung Park ◽  
Hae Min So ◽  
Ki Hyun Kim ◽  
...  

Ulmus species have been widely used in Korean folk medicine because of their anti-inflammatory and antimicrobial properties. We intended to investigate the wound healing effect of the powder of Ulmus parvifolia (UP) root bark in a mouse wound healing model. We also determined the mechanisms of effects of Ulmus parvifolia (UP) in skin and skin wound healing effect using keratinocyte model. in vivo experiments showed that the wound lesions in the mice decreased by U. parvifolia with 200 mesh size of root bark powder and significantly reduced by treatment with UP, compared with those treated with U. macrocarpa (UM). Results from in vitro experiments also revealed that UP extract promoted the migration of human skin keratinocytes. UP powder treatment upregulated the expression of the matrix metalloproteinase-2 and -9 protein and significantly increased transforming growth factor (TGF)-β levels. We confirmed that topical administration of the bark powder of exerted a significant effect on skin wound healing by upregulating the expression of MMP and transforming growth factor-β. TGF-β In, Our study suggests that U. parvifolia may be a potential candidate for skin wound healing including epidermal skin rejuvernation.


2016 ◽  
Vol 18 (4) ◽  
pp. 411-419 ◽  
Author(s):  
Eva L. Arantes ◽  
Nathalia Dragano ◽  
Albina Ramalho ◽  
Daniele Vitorino ◽  
Gabriela F. de-Souza ◽  
...  

Background: The development of methods for improving skin wound healing may have an impact on the outcomes of a number of medical conditions. The topical use of polyunsaturated fatty acids (PUFAs) can accelerate skin wound healing through mechanisms that involve, at least in part, the modulation of inflammatory activity. Purpose: We evaluated whether G-protein-coupled receptor 120 (GPR120), a recently identified receptor for docosahexaenoic acid (DHA) with anti-inflammatory activity, is expressed in the skin and responds to topical DHA. Method: Male Wistar rats were submitted to an 8.0-mm wound on the back and were immediately administered a topical treatment of a solution containing 30 μM of DHA once a day. The healing process was photodocumented, and tissues were collected on Days 5, 9, and 15 for protein and RNA analyses and histological evaluation. Results: GPR120 was expressed in the intact skin and in the wound. Keratinocytes expressed the most skin GPR120, while virtually no expression was detected in fibroblasts. Upon DHA topical treatment, wound healing was significantly accelerated and was accompanied by the molecular activation of GPR120, as determined by its association with β-arrestin-2. In addition, DHA promoted a reduction in the expression of interleukin (IL) 1β and an increase in the expression of IL-6. Furthermore, there was a significant increase in expression of transforming growth factor β (TGF-β) and the keratinocyte marker involucrin. Discussion: Topical DHA improved skin wound healing. The activation of GPR120 is potentially involved in this process.


2020 ◽  
Author(s):  
Sylwia Machcinska ◽  
Marta Kopcewicz ◽  
Joanna Bukowska ◽  
Katarzyna Walendzik ◽  
Barbara Gawronska-Kozak

ABSTRACTHypoxia and hypoxia-regulated factors [e. g., hypoxia-inducible factor-1α (Hif-1α), factor inhibiting Hif-1α (Fih-1), thioredoxin-1 (Trx-1), aryl hydrocarbon receptor nuclear translocator 2 (Arnt-2)] have essential roles in skin wound healing. Using Foxn1−/− mice that can heal skin injuries in a unique scarless manner, we investigated the interaction between Foxn1 and hypoxia-regulated factors. The Foxn1−/− mice displayed impairments in the regulation of Hif-1α, Trx-1 and Fih-1 but not Arnt-2 during the healing process. An analysis of wounded skin showed that the skin of the Foxn1−/− mice healed in a scarless manner, displaying rapid re-epithelialization and an increase in transforming growth factor β (Tgfβ-3) and collagen III expression. An in vitro analysis revealed that Foxn1 overexpression in keratinocytes isolated from the skin of the Foxn1−/− mice led to reduced Hif-1α expression in normoxic but not hypoxic cultures and inhibited Fih-1 expression exclusively under hypoxic conditions. These data indicate that in the skin, Foxn1 affects hypoxia-regulated factors that control the wound healing process and suggest that under normoxic conditions, Foxn1 is a limiting factor for Hif-1α.


2019 ◽  
Vol 9 (1) ◽  
pp. 59
Author(s):  
Min Cheol Kang ◽  
Silvia Yumnam ◽  
Woo Sung Park ◽  
Hae Min So ◽  
Ki Hyun Kim ◽  
...  

Ulmus parvifolia is one of the medicinal plants used traditionally for treatment of wounds. We intended to investigate the wound healing effect of the powder of Ulmus parvifolia (UP) root bark in a mouse wound healing model. We also determined the mechanisms of effects of U. parvifolia in skin and skin wound healing effects using a keratinocyte model. Animal experiments showed that the wound lesions in the mice decreased with 200 mesh U. parvifolia root bark powder and were significantly reduced with treatment by UP, compared with those treated with Ulmus macrocarpa (UM). Results from in vitro experiments also revealed that UP extract promoted the migration of human skin keratinocytes. UP powder treatment upregulated the expression of the matrix metalloproteinase-2 and -9 protein and significantly increased transforming growth factor (TGF)-β levels. We confirmed that topical administration of the bark powder exerted a significant effect on skin wound healing by upregulating the expression of MMP and transforming growth factor-β. Our study suggests that U. parvifolia may be a potential candidate for skin wound healing including epidermal skin rejuvenation.


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