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.

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.

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.

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