scholarly journals A “traffic control” role for TGFβ3: orchestrating dermal and epidermal cell motility during wound healing

2006 ◽  
Vol 172 (7) ◽  
pp. 1093-1105 ◽  
Author(s):  
Balaji Bandyopadhyay ◽  
Jianhua Fan ◽  
Shengxi Guan ◽  
Yong Li ◽  
Mei Chen ◽  
...  
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Epidermal Cell ◽  
Traffic Control ◽  
Transforming Growth Factor ◽  
Skin Wound ◽  
Epidermal Cells ◽  
Skin Wound Healing ◽  
Tgfβ Receptor ◽  
Dermal Cells

Cell migration is a rate-limiting event in skin wound healing. In unwounded skin, cells are nourished by plasma. When skin is wounded, resident cells encounter serum for the first time. As the wound heals, the cells experience a transition of serum back to plasma. In this study, we report that human serum selectively promotes epidermal cell migration and halts dermal cell migration. In contrast, human plasma promotes dermal but not epidermal cell migration. The on-and-off switch is operated by transforming growth factor (TGF) β3 levels, which are undetectable in plasma and high in serum, and by TGFβ receptor (TβR) type II levels, which are low in epidermal cells and high in dermal cells. Depletion of TGFβ3 from serum converts serum to a plasmalike reagent. The addition of TGFβ3 to plasma converts it to a serumlike reagent. Down-regulation of TβRII in dermal cells or up-regulation of TβRII in epidermal cells reverses their migratory responses to serum and plasma, respectively. Therefore, the naturally occurring plasma→serum→plasma transition during wound healing orchestrates the orderly migration of dermal and epidermal cells.

scholarly journals Transforming Growth Factor α (TGFα)-Stimulated Secretion of HSP90α: Using the Receptor LRP-1/CD91 To Promote Human Skin Cell Migration against a TGFβ-Rich Environment during Wound Healing

2008 ◽  
Vol 28 (10) ◽  
pp. 3344-3358 ◽  
Author(s):  
Chieh-Fang Cheng ◽  
Jianhua Fan ◽  
Mark Fedesco ◽  
Shengxi Guan ◽  
Yong Li ◽  
...  
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Ldl Receptor ◽  
Skin Wound ◽  
Skin Wound Healing ◽  
Transforming Growth Factor Α ◽  
Dermal Cell ◽  
Factor Α

ABSTRACT Jump-starting and subsequently maintaining epidermal and dermal cell migration are essential processes for skin wound healing. These events are often disrupted in nonhealing wounds, causing patient morbidity and even fatality. Currently available treatments are unsatisfactory. To identify novel wound-healing targets, we investigated secreted molecules from transforming growth factor α (TGFα)-stimulated human keratinoytes, which contained strong motogenic, but not mitogenic, activity. Protein purification allowed us to identify the heat shock protein 90α (hsp90α) as the factor fully responsible for the motogenic activity in keratinocyte secretion. TGFα causes rapid membrane translocation and subsequent secretion of hsp90α via the unconventional exosome pathway in the cells. Secreted hsp90α promotes both epidermal and dermal cell migration through the surface receptor LRP-1 (LDL receptor-related protein 1)/CD91. The promotility activity resides in the middle domain plus the charged sequence of hsp90α but is independent of the ATPase activity. Neutralizing the extracellular function of hsp90α blocks TGFα-induced keratinicyte migration. Most intriguingly, unlike the effects of canonical growth factors, the hsp90α signaling overrides the inhibition of TGFβ, an abundant inhibitor of dermal cell migration in skin wounds. This finding provides a long-sought answer to the question of how dermal cells migrate into the wound environment to build new connective tissues and blood vessels. Thus, secreted hsp90α is potentially a new agent for wound healing.

Juglone ameliorates skin wound healing by promoting skin cell migration through Rac1/Cdc42/PAK pathway

2016 ◽  
Vol 24 (5) ◽  
pp. 786-794 ◽  
Author(s):  
Hussain M. Wahedi ◽  
Yong U. Park ◽  
Eun-Yi Moon ◽  
Sun Y. Kim
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Skin Wound ◽  
Skin Wound Healing ◽  
Skin Cell

Rapid epithelialisation of fetal wounds is associated with the early deposition of tenascin

1991 ◽  
Vol 99 (3) ◽  
pp. 583-586 ◽  
Author(s):  
D.J. Whitby ◽  
M.T. Longaker ◽  
M.R. Harrison ◽  
N.S. Adzick ◽  
M.W. Ferguson
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Temporal Distribution ◽  
Cell Types ◽  
Skin Wound ◽  
Skin Wound Healing ◽  
Early Appearance ◽  
Complex Process ◽  
Healing Wounds ◽  
Fetal Wound

Wound healing is a complex process involving the interaction of many cell types with the extracellular matrix (ECM). Fetal skin wound healing differs from that in the adult in that it occurs rapidly and without scar formation. The mechanisms underlying these differing processes may be related to the fetal environment, the stage of differentiation of the fetal cells or the ECM deposited in the wound. The spatial and temporal distribution of two components of the ECM, fibronectin and tenascin, were studied by immunostaining of cryosections from trunk wounds of fetal and adult sheep. Epithelialisation was complete earlier in the fetal wound than in the adult. The distribution of fibronectin was similar in fetal and adult wounds but tenascin was present earlier in the fetal wound. Fibronectin has several roles in wound healing including acting as a substratum for cell migration and as a mediator of cell adhesion through cell surface integrins. The attachment of fibroblasts to fibronectin is inhibited by tenascin and during development the appearance of tenascin in the ECM of migratory pathways correlates with the initiation of cell migration. Similarly, the appearance of tenascin in healing wounds may initiate cell migration. Tenascin was present in these wounds prior to cell migration and the rapid epithelialisation of fetal wounds may be due to the early appearance of tenascin in the wound.

scholarly journals The effect of earthworm extract on promoting skin wound healing

2018 ◽  
Vol 38 (2) ◽  
Author(s):  
Zhen-han Deng ◽  
Jian-jian Yin ◽  
Wei Luo ◽  
Ronak Naveenchandra Kotian ◽  
Shan-shan Gao ◽  
...  
Keyword(s):  
Wound Healing ◽  
Healthcare System ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
White Blood Cells ◽  
Skin Wound ◽  
Wound Healing Process ◽  
Blood Capillary ◽  
Skin Wound Healing

Chronic nonhealing wounds pose a significant challenge to healthcare system because of its tremendous utilization of resources and time to heal. It has a well-deserved reputation for reducing the quality of life for those affected and represent a substantial economic burden to the healthcare system overall. Earthworms are used as a traditional Chinese medicine, and have been applied pharmacologically and clinically since a long time in China. However, there is paucity in data regarding its wound healing effects. Therefore, we investigated the effect of earthworm extract (EE) on skin wound healing process. The obtained data showed that EE has healing effects on local wound of mice. It decreased the wound healing time and reduced the ill-effects of inflammation as determined by macroscopic, histopathologic, hematologic, and immunohistochemistry parameters. The potential mechanism could be accelerated hydroxyproline and transforming growth factor-β secretion—thus increasing the synthesis of collagen, promoting blood capillary, and fibroblast proliferation. It could accelerate the removal of necrotic tissue and foreign bodies by speeding up the generation of interleukin-6, white blood cells, and platelets. It thus enhances immunity, reduces the risk of infection, and promotes wound healing. All in all, the obtained data demonstrated that EE improves quality of healing and could be used as a propitious wound healing agent.

scholarly journals Ulmus Parvifolia Accelerate Skin Wound Healing by Regulating the Expression of MMPs and TGF-β

2019 ◽  
Author(s):  
Min Cheol Kang ◽  
Silvia Yumnam ◽  
Woo Sung Park ◽  
Hae Min So ◽  
Ki Hyun Kim ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Skin Wound ◽  
Root Bark ◽  
Potential Candidate ◽  
Skin Wound Healing ◽  
Healing Effect ◽  
Ulmus Parvifolia ◽  
Wound Healing Effect

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.

scholarly journals 4-aminopyridine promotes accelerated skin wound healing

2021 ◽  
Author(s):  
Jagadeeshaprasad Mashanipalya ◽  
Prem Kumar Govindappa ◽  
Amanda Nelson ◽  
Mark Noble ◽  
John Elfar
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Wound Closure ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Transforming Growth Factor Β ◽  
Skin Wound ◽  
Skin Wound Healing ◽  
S 100 ◽  
Skin Healing

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.

Myostatin-null mice exhibit delayed skin wound healing through the blockade of transforming growth factor-β signaling by decorin

2012 ◽  
Vol 302 (8) ◽  
pp. C1213-C1225 ◽  
Author(s):  
Chen Zhang ◽  
Chek Kun Tan ◽  
Craig McFarlane ◽  
Mridula Sharma ◽  
Nguan Soon Tan ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Wound Repair ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Critical Role ◽  
Transforming Growth Factor Β ◽  
Skin Wound ◽  
Wound Healing Process ◽  
Skin Wound Healing

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.

Topical Docosahexaenoic Acid (DHA) Accelerates Skin Wound Healing in Rats and Activates GPR120

2016 ◽  
Vol 18 (4) ◽  
pp. 411-419 ◽  
Author(s):  
Eva L. Arantes ◽  
Nathalia Dragano ◽  
Albina Ramalho ◽  
Daniele Vitorino ◽  
Gabriela F. de-Souza ◽  
...  
Keyword(s):  
Wound Healing ◽  
Docosahexaenoic Acid ◽  
Topical Treatment ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Transforming Growth Factor Β ◽  
Skin Wound ◽  
Inflammatory Activity ◽  
Histological Evaluation ◽  
Skin Wound Healing

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.

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