scholarly journals A central role for vimentin in regulating repair function during healing of the lens epithelium

2014 ◽  
Vol 25 (6) ◽  
pp. 776-790 ◽  
Author(s):  
A. S. Menko ◽  
B. M. Bleaken ◽  
A. A. Libowitz ◽  
L. Zhang ◽  
M. A. Stepp ◽  
...  

Mock cataract surgery provides a unique ex vivo model for studying wound repair in a clinically relevant setting. Here wound healing involves a classical collective migration of the lens epithelium, directed at the leading edge by an innate mesenchymal subpopulation of vimentin-rich repair cells. We report that vimentin is essential to the function of repair cells as the directors of the wound-healing process. Vimentin and not actin filaments are the predominant cytoskeletal elements in the lamellipodial extensions of the repair cells at the wound edge. These vimentin filaments link to paxillin-containing focal adhesions at the lamellipodial tips. Microtubules are involved in the extension of vimentin filaments in repair cells, the elaboration of vimentin-rich protrusions, and wound closure. The requirement for vimentin in repair cell function is revealed by both small interfering RNA vimentin knockdown and exposure to the vimentin-targeted drug withaferin A. Perturbation of vimentin impairs repair cell function and wound closure. Coimmunoprecipitation analysis reveals for the first time that myosin IIB is associated with vimentin, linking vimentin function in cell migration to myosin II motor proteins. These studies reveal a critical role for vimentin in repair cell function in regulating the collective movement of the epithelium in response to wounding.

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.


Author(s):  
Ahmed G. Hegazi ◽  
Faiz M. Al Guthami ◽  
Mohamed H. Basiouny ◽  
Ahmed F.M. Al Gethami

Honey has been documented as the oldest traditional medicine. It has been effective in suppressing inflammation, wound repair enhancer, and rapid autolytic debridement. The aim of this investigation was to evaluate the role of Saudi Arabia Talh honey (Acacia nilotica) dressing as a good alternative in care of diabetic foot (DFU) healing activity for twenty patients, wound total bacterial count, and serum cytokines levels (IFN-γ, IL-1, and IL-6). The results showed that Talh honey stimulates the wound healing process, broad-spectrum antibacterial activity, and reduction in the proinflammatory cytokines IFN-γ, IL-1, and IL-6 levels. It could be concluded that Talh honey bioactivities enhance wound healing by promoting tissue growth leading to wound repair, antibacterial, and reduction of inflammation.


2020 ◽  
Author(s):  
Daisuke Ito ◽  
Hiroyasu Ito ◽  
Takayasu Ideta ◽  
Ayumu Kanbe ◽  
Soranobu Ninomiya ◽  
...  

Abstract Background The skin wound healing process is regulated by various cytokines, chemokines, and growth factors. Recent reports have demonstrated that spermine/spermidine (SPD) promote wound healing through urokinase-type plasminogen activator (uPA)/uPA receptor (uPAR) signaling in vitro. Here, we investigated whether the systemic and topical administration of SPD would accelerate the skin wound-repair process in vivo.Methods A skin wound repair model was established using C57BL/6 J mice. SPD was mixed with white petrolatum for topical administration. For systemic administration, SPD mixed with drinking water was orally administered. Changes in wound size over time were calculated using digital photography.Results Systemic and topical SPD treatment significantly accelerated skin wound healing. The administration of SPD promoted the uPA/uPAR pathway in wound sites. Moreover, topical treatment with SPD enhanced the expression of IL-6 and TNF-α in wound sites. Scratch and cell proliferation assays revealed that SPD administration accelerated scratch wound closure and cell proliferation in vitro.Conclusion These results indicate that treatment with SPD promotes skin wound healing through activation of the uPA/uPAR pathway and induction of the inflammatory response in wound sites. The administration of SPD might contribute to new effective treatments to accelerate skin wound healing.


2021 ◽  
Author(s):  
Mary Yinghua Zhang ◽  
Shuyi Fang ◽  
Hongyu Gao ◽  
Xiaoli Zhang ◽  
Dongsheng Gu ◽  
...  

ABSTRACTWe report our discovery of an important player in the development of skin fibrosis, a hallmark of scleroderma. Scleroderma is a fibrotic disease, affecting 70,000 to 150,000 Americans. Fibrosis is a pathological wound healing process that produces an excessive extracellular matrix to interfere with normal organ function. Fibrosis contributes to nearly half of human mortality. Scleroderma has heterogeneous phenotypes, unpredictable outcomes, no validated biomarkers, and no effective treatment. Thus, strategies to slow down scleroderma progression represent an urgent medical need. While a pathological wound healing process like fibrosis leaves scars and weakens organ function, oral mucosa wound healing is a scarless process. After re-analyses of gene expression datasets from oral mucosa wound healing and skin fibrosis, we discovered that several pathways constitutively activated in skin fibrosis are transiently induced during oral mucosa wound healing process, particularly the amphiregulin (Areg) gene. Areg expression is upregulated ~10 folds 24hrs after oral mucosa wound but reduced to the basal level 3 days later. During bleomycin-induced skin fibrosis, a commonly used mouse model for skin fibrosis, Areg is up-regulated throughout the fibrogenesis and is associated with elevated cell proliferation in the dermis. To demonstrate the role of Areg for skin fibrosis, we used mice with Areg knockout, and found that Areg deficiency essentially prevents bleomycin-induced skin fibrosis. We further determined that bleomycin-induced cell proliferation in the dermis was not observed in the Areg null mice. Furthermore, we found that inhibiting MEK, a downstream signaling effector of Areg, by selumetinib also effectively blocked bleomycin-based skin fibrosis model. Based on these results, we concluded that the Areg-EGFR-MEK signaling axis is critical for skin fibrosis development. Blocking this signaling axis may be effective in treating scleroderma.


2019 ◽  
Vol 34 (8) ◽  
pp. 1171-1187
Author(s):  
Farnoush Oveissi ◽  
Naser Tavakoli ◽  
Mohsen Minaiyan ◽  
Mohammad Reza Mofid ◽  
Azade Taheri

Epidermal lipoxygenase enzyme extracted from Ambystoma mexicanum (AmbLOXe) is known to accelerate the wound-healing process. AmbLOXe as a protein suffers from inactivation and losing its activity during formulation. Therefore, a delivery system that protects AmbLOXe from inactivation and preserves its activity is needed. We prepared AmbLOXe-loaded pectin nanoparticles (AmbLOXe Pec-NPs) and placed them into an alginate hydrogel. AmbLOXe Pec-NPs incorporation into the alginate hydrogel provides a means for controlled and sustained delivery of AmbLOXe to the wound site. Furthermore, the suitable swelling behavior and mechanical properties of AmbLOXe Pec-NPs alginate hydrogel make it feasible for clinical use. AmbLOXe Pec-NPs alginate hydrogel significantly enhanced the wound-healing process on the rat full-thickness excisional wounds, increased the rate of wound closure, enhanced the re-epithelialization and decreased the incidence of abnormal scarring. AmbLOXe Pec-NPs alginate hydrogel can be proposed as an effective wound hydrogel for improving wound healing with minimal scarring.


2019 ◽  
Vol 81 (4) ◽  
Author(s):  
Ulfah Anwar ◽  
Siti Pauliena Mohd Bohari

The aim of this research is to investigate the wound healing process in in vitro by combining the Manihot esculenta aqueous extract and therapeutic ultrasound. Firstly, the optimization seeding densities of HSF cell 1184 in six-well plate, and then followed by the scratch assay experiment. The scratched that made was treated with the remedial treatments (Manihot esculenta aqueous extract only; ascorbic acid+ therapeutic ultrasound; Manihot esculenta aqueous extract+ ascorbic acid; Manihot esculenta aqueous extract+ therapeutic ultrasound and also the combination of these three materials). The rate of wound closure was observed and analysed at a time interval of 0, 2, 4, 6, 8, 10 and 24 h by using image J software. Then, the cells viability were analysed using the MTT assay. The result showed that Manihot esculenta aqueous extract coupled with specific dose therapeutic ultrasound represents a significantly high rate of wound closure at 96.10 % with the cell numbers at 5.44×105 cells/mL when compared to the other combination therapy. The finding of this study revealed that Manihot esculenta aqueous extract 200 µg/mL and the therapeutic ultrasound specific dose (3 MHz, 300 mWatt/cm2, 50% in 5 min) have the potential in accelerating wound healing process of cells in in vitro.


2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Sushant Kumar Das ◽  
Yi Feng Yuan ◽  
Mao Quan Li

To explore whether or not inhibition of protein kinase C βII (PKC βII) stimulates angiogenesis as well as prevents excessive NETosis in diabetics thus accelerating wound healing. Streptozotocin (STZ, 60 mg/kg/day for 5 days, i.p.) was injected to induce type I diabetes in male ICR mice. Mice were treated with ruboxistaurin (30 mg/kg/day, orally) for 14 consecutive days. Wound closure was evaluated by wound area and number of CD31-stained capillaries. Peripheral blood flow cytometry was done to evaluate number of circulating endothelial progenitor cells (EPCs). NETosis assay and wound tissue immunofluorescence imaging were done to evaluate the percentage of neutrophils undergoing NETosis. Furthermore, the expression of PKC βII, protein kinase B (Akt), endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), and histone citrullation (H3Cit) were determined in the wound by Western blot analysis. Ruboxistaurin accelerated wound closure and stimulated angiogenesis in diabetic mice. The number of circulating EPCs was increased significantly in ruboxistaurin-treated diabetic mice. Moreover, ruboxistaurin treatment significantly decreases the percentages of H3Cit+ cells in both peripheral blood and wound areas. This prevented excess activated neutrophils forming an extracellular trap (NETs) formation. The expressions of phospho-Akt (p-Akt), phospho-eNOS (p-eNOS), and VEGF increased significantly in diabetic mice on ruboxistaurin treatment. The expressions of PKC βII and H3Cit+, on the other hand, decreased with ruboxistaurin treatment. The results of the present study suggest that ruboxistaurin by inhibiting PKC βII activation, reverses EPCs dysfunction as well as prevents exaggerated NETs formation in a diabetic mouse model; thereby accelerating the wound healing process.


2015 ◽  
Vol 77 (6) ◽  
Author(s):  
Nur Adilah Abd Rahman ◽  
Mamman Hassan Buhari ◽  
M. Mahadi Abdul Jamil

Electroporation (EP) is a method of controlling cell function by using pulses of electrical fields to create pore through a cell membrane and causes other substance around it to be absorbed into the cell. Where This method had been led to variety of medical applications. While, microcontact printing (μCP) is a quite useful technique for patterning extracellular matrix as an adhesion molecule for cells that works for controlling the cell growth. This study focuses on reviewing the basic concepts and techniques of electroporation and Microcontact printing, as applied to molecular biology & cancer treatment. The combination of these two technique might be a new technique for wound healing process treatment.


2020 ◽  
Vol 45 (6) ◽  
Author(s):  
I. A. Ajayi ◽  
O. B. Omolere

This study investigated the wound healing potential of hexane and methanolic seed extracts of Azadirachta indica using 35 wistar rats that were divided into 5 groups of 7 rats each. Phytochemical screening and antimicrobial activity of the extracts were carried out while the wound healing potential was evaluated by treating the test rats with 5 % and 10 % hexane and methanol extracts in an experiment that lasted for 21 days. Wound area and percentage of wound closure of the rats were noted at four-day intervals and at 21 days, the blood and organs of the rats were subjected to haematological and histopathological analyses respectively. The extracts were found to contain tannins, glycosides and phenols and they inhibited the growth of tested organisms. All the test rats displayed better and faster healing than the control ones but there were no significant differences between their haematological and histophatological results. The seed extracts quickened the wound healing process of the rats and might therefore be useful in wound treatment.


Sign in / Sign up

Export Citation Format

Share Document