scholarly journals Human skin long noncoding RNA WAKMAR1 regulates wound healing by enhancing keratinocyte migration

2019 ◽  
Vol 116 (19) ◽  
pp. 9443-9452 ◽  
Author(s):  
Dongqing Li ◽  
Lara Kular ◽  
Manika Vij ◽  
Eva K. Herter ◽  
Xi Li ◽  
...  
Keyword(s):  
Wound Healing ◽  
Noncoding Rna ◽  
Chronic Wounds ◽  
Ex Vivo ◽  
Dna Methyltransferases ◽  
Skin Wound ◽  
Skin Wound Healing ◽  
Protein Coding ◽  
Keratinocyte Migration ◽  
Gene Expression Control

An increasing number of studies reveal the importance of long noncoding RNAs (lncRNAs) in gene expression control underlying many physiological and pathological processes. However, their role in skin wound healing remains poorly understood. Our study focused on a skin-specific lncRNA, LOC105372576, whose expression was increased during physiological wound healing. In human nonhealing wounds, however, its level was significantly lower compared with normal wounds under reepithelialization. We characterized LOC105372576 as a nuclear-localized, RNAPII-transcribed, and polyadenylated lncRNA. In keratinocytes, its expression was induced by TGF-β signaling. Knockdown of LOC105372576 and activation of its endogenous transcription, respectively, reduced and increased the motility of keratinocytes and reepithelialization of human ex vivo skin wounds. Therefore, LOC105372576 was termed “wound and keratinocyte migration-associated lncRNA 1” (WAKMAR1). Further study revealed that WAKMAR1 regulated a network of protein-coding genes important for cell migration, most of which were under the control of transcription factor E2F1. Mechanistically, WAKMAR1 enhanced E2F1 expression by interfering with E2F1 promoter methylation through the sequestration of DNA methyltransferases. Collectively, we have identified a lncRNA important for keratinocyte migration, whose deficiency may be involved in the pathogenesis of chronic wounds.

scholarly journals The Effect of a Polyester Nanofibrous Membrane with a Fibrin-Platelet Lysate Coating on Keratinocytes and Endothelial Cells in a Co-Culture System

Nanomaterials ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 457
Author(s):  
Andreu Blanquer ◽  
Jana Musilkova ◽  
Elena Filova ◽  
Johanka Taborska ◽  
Eduard Brynda ◽  
...  
Keyword(s):  
Wound Healing ◽  
Endothelial Cells ◽  
Chronic Wounds ◽  
Human Keratinocytes ◽  
Skin Wound ◽  
Platelet Lysate ◽  
Therapeutic Approaches ◽  
Skin Wound Healing ◽  
New Therapeutic Approaches ◽  
Proliferation And Differentiation

Chronic wounds affect millions of patients worldwide, and it is estimated that this number will increase steadily in the future due to population ageing. The research of new therapeutic approaches to wound healing includes the development of nanofibrous meshes and the use of platelet lysate (PL) to stimulate skin regeneration. This study considers a combination of a degradable electrospun nanofibrous blend of poly(L-lactide-co-ε-caprolactone) and poly(ε-caprolactone) (PLCL/PCL) membranes (NF) and fibrin loaded with various concentrations of PL aimed at the development of bioactive skin wound healing dressings. The cytocompatibility of the NF membranes, as well as the effect of PL, was evaluated in both monocultures and co-cultures of human keratinocytes and human endothelial cells. We determined that the keratinocytes were able to adhere on all the membranes, and their increased proliferation and differentiation was observed on the membranes that contained fibrin with at least 50% of PL (Fbg + PL) after 14 days. With respect to the co-culture experiments, the membranes with fibrin with 20% of PL were observed to enhance the metabolic activity of endothelial cells and their migration, and the proliferation and differentiation of keratinocytes. The results suggest that the newly developed NF combined with fibrin and PL, described in the study, provides a promising dressing for chronic wound healing purposes.

scholarly journals EFFECTS OF PROBIOTICS SUPPLEMENTATION ON SKIN WOUND HEALING IN DIABETIC RATS

2020 ◽  
Vol 33 (1) ◽  
Author(s):  
Letícia Fuganti CAMPOS ◽  
Eliane TAGLIARI ◽  
Thais Andrade Costa CASAGRANDE ◽  
Lúcia de NORONHA ◽  
Antônio Carlos L. CAMPOS ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Wound Healing ◽  
Type I Collagen ◽  
Chronic Wounds ◽  
Skin Wound ◽  
Diabetic Rats ◽  
Control Group ◽  
Type I ◽  
Collagen Deposition ◽  
Skin Wound Healing

ABSTRACT Background: Chronic wounds in patients with Diabetes Mellitus often become incurable due to prolonged and excessive production of inflammatory cytokines. The use of probiotics modifies the intestinal microbiota and modulates inflammatory reactions. Aim: To evaluate the influence of perioperative supplementation with probiotics in the cutaneous healing process in diabetic rats. Methods: Forty-six rats were divided into four groups (C3, P3, C10, P10) according to the treatment (P=probiotic or C=control, both orally administered) and day of euthanasia, 3rd or 10th postoperative days. All rats were induced to Diabetes Mellitus 72 h before starting the experiment with alloxan. Supplementation was initiated five days before the incision and maintained until euthanasia. Scalpel incision was guided by a 2x2 cm mold and the wounds were left to heal per second-intention. The wounds were digitally measured. Collagen densitometry was done with Picrosirius Red staining. Histological parameters were analyzed by staining by H&E. Results: The contraction of the wound was faster in the P10 group which resulted in a smaller scar area (p=0.011). There was an increase in type I collagen deposition from the 3rd to the 10th postoperative day in the probiotic groups (p=0.016), which did not occur in the control group (p=0.487). The histological analysis showed a better degree of healing in the P10 group (p=0.005), with fewer polymorphonuclear (p<0.001) and more neovessels (p=0.001). Conclusions: Perioperative supplementation of probiotics stimulates skin wound healing in diabetic rats, possibly due to attenuation of the inflammatory response and increased neovascularization and type I collagen deposition.

scholarly journals Platelet-rich plasma accelerates skin wound healing by promoting re-epithelialization

2020 ◽  
Vol 8 ◽  
Author(s):  
Pengcheng Xu ◽  
Yaguang Wu ◽  
Lina Zhou ◽  
Zengjun Yang ◽  
Xiaorong Zhang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Wound Repair ◽  
Chronic Wounds ◽  
Platelet Rich Plasma ◽  
Skin Wound ◽  
Local Inflammation ◽  
Skin Wound Healing

Abstract Background Autologous platelet-rich plasma (PRP) has been suggested to be effective for wound healing. However, evidence for its use in patients with acute and chronic wounds remains insufficient. The aims of this study were to comprehensively examine the effectiveness, synergy and possible mechanism of PRP-mediated improvement of acute skin wound repair. Methods Full-thickness wounds were made on the back of C57/BL6 mice. PRP or saline solution as a control was administered to the wound area. Wound healing rate, local inflammation, angiogenesis, re-epithelialization and collagen deposition were measured at days 3, 5, 7 and 14 after skin injury. The biological character of epidermal stem cells (ESCs), which reflect the potential for re-epithelialization, was further evaluated in vitro and in vivo. Results PRP strongly improved skin wound healing, which was associated with regulation of local inflammation, enhancement of angiogenesis and re-epithelialization. PRP treatment significantly reduced the production of inflammatory cytokines interleukin-17A and interleukin-1β. An increase in the local vessel intensity and enhancement of re-epithelialization were also observed in animals with PRP administration and were associated with enhanced secretion of growth factors such as vascular endothelial growth factor and insulin-like growth factor-1. Moreover, PRP treatment ameliorated the survival and activated the migration and proliferation of primary cultured ESCs, and these effects were accompanied by the differentiation of ESCs into adult cells following the changes of CD49f and keratin 10 and keratin 14. Conclusion PRP improved skin wound healing by modulating inflammation and increasing angiogenesis and re-epithelialization. However, the underlying regulatory mechanism needs to be investigated in the future. Our data provide a preliminary theoretical foundation for the clinical administration of PRP in wound healing and skin regeneration.

Plasmin/plasminogen is essential for the healing of tympanic membrane perforations

2006 ◽  
Vol 96 (10) ◽  
pp. 512-519 ◽  
Author(s):  
Jinan Li ◽  
Per-Olof Eriksson ◽  
Annika Hansson ◽  
Sten Hellström ◽  
Tor Ny
Keyword(s):  
Wound Healing ◽  
Tympanic Membrane ◽  
Healing Process ◽  
Inflammatory Cells ◽  
Skin Wound ◽  
Skin Wound Healing ◽  
Keratinocyte Migration ◽  
Tympanic Membrane Perforations ◽  
Wounded Area ◽  
Deficient Mice

SummaryPlasminogen has been proposed to play an important role in different tissue remodeling processes such as wound healing and tissue regeneration after injuries. The healing of tympanic membrane perforations is a well-organized chain of inflammatory events, with an initial invasion of inflammatory cells followed by reparative and restoration phases. Here we show that the healing of tympanic membrane perforations is completely arrested in plasminogen-deficient mice, with no signs of any healing even 143 days after perforation. Inflammatory cells were recruited to the wounded area, but there were no signs of tissue debridement. In addition, removal of fibrin, keratinocyte migration and in-growth of connective tissue were impaired. This contrasts with skin wound healing, where studies have shown that, although the healing process is delayed, it reaches completion in all plasminogen-deficient mice. Our finding that keratinocyte migration and re-epithelialization were completely arrested in plasminogen-deficient mice indicates that plasminogen/plasmin plays a more profound role in the healing of tympanic membrane perforations than in the healing of other epithelial wounds.

scholarly journals JMJD3 and NF-κB-dependent activation of Notch1 gene is required for keratinocyte migration during skin wound healing

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Jungtae Na ◽  
Jee Yoon Shin ◽  
Hayan Jeong ◽  
Jee Youn Lee ◽  
Beom Joon Kim ◽  
...  
Keyword(s):  
Wound Healing ◽  
Skin Wound ◽  
Skin Wound Healing ◽  
Keratinocyte Migration

scholarly journals Immunomodulatory Properties of Host Defence Peptides in Skin Wound Healing

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 952
Author(s):  
Marija Petkovic ◽  
Michelle Vang Mouritzen ◽  
Biljana Mojsoska ◽  
Håvard Jenssen
Keyword(s):  
Wound Healing ◽  
Molecular Mechanisms ◽  
Chronic Wounds ◽  
Skin Wound ◽  
Host Defence ◽  
Large Network ◽  
Skin Wound Healing ◽  
Signalling Molecules ◽  
Inflammatory Conditions ◽  
Peripheral Sensory

Cutaneous wound healing is a vital biological process that aids skin regeneration upon injury. Wound healing failure results from persistent inflammatory conditions observed in diabetes, or autoimmune diseases like psoriasis. Chronic wounds are incurable due to factors like poor oxygenation, aberrant function of peripheral sensory nervature, inadequate nutrients and blood tissue supply. The most significant hallmark of chronic wounds is heavily aberrant immune skin function. The immune response in humans relies on a large network of signalling molecules and their interactions. Research studies have reported on the dual role of host defence peptides (HDPs), which are also often called antimicrobial peptides (AMPs). Their duality reflects their potential for acting as antibacterial peptides, and as immunodulators that assist in modulating several biological signalling pathways related to processes such as wound healing, autoimmune disease, and others. HDPs may differentially control gene regulation and alter the behaviour of epithelial and immune cells, resulting in modulation of immune responses. In this review, we shed light on the understanding and most recent advances related to molecular mechanisms and immune modulatory features of host defence peptides in human skin wound healing. Understanding their functional role in skin immunity may further inspire topical treatments for chronic wounds.

scholarly journals TET2-interacting long noncoding RNA promotes active DNA demethylation of the MMP-9 promoter in diabetic wound healing

2019 ◽  
Vol 10 (11) ◽  
Author(s):  
Liyan Zhou ◽  
Meng Ren ◽  
Tingting Zeng ◽  
Wei Wang ◽  
Xiaoyi Wang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Excision Repair ◽  
Skin Wound ◽  
Dna Demethylation ◽  
Skin Wound Healing ◽  
Active Dna Demethylation ◽  
Diabetic Wound Healing ◽  
Base Excision

Abstract Wound healing in diabetic skin is impaired by excessive activation of matrix metalloproteinase-9 (MMP-9). MMP-9 transcription is activated by Ten-eleven translocation 2 (TET2), a well-known DNA demethylation protein that induces MMP-9 promoter demethylation in diabetic skin tissues. However, how TET2 is targeted to specific loci in the MMP-9 promoter is unknown. Here, we identified a TET2-interacting long noncoding RNA (TETILA) that is upregulated in human diabetic skin tissues. TETILA regulates TET2 subcellular localization and enzymatic activity, indirectly activating MMP-9 promoter demethylation. TETILA also recruits thymine-DNA glycosylase (TDG), which simultaneously interacts with TET2, for base excision repair-mediated MMP-9 promoter demethylation. Together, our results suggest that the TETILA serves as a genomic homing signal for TET2-mediated demethylation specific loci in MMP-9 promoter, thereby disrupting the process of diabetic skin wound healing.

scholarly journals Hyperglycemia-Induced Changes in Hyaluronan Contribute to Impaired Skin Wound Healing in Diabetes: Review and Perspective

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Sajina Shakya ◽  
Yan Wang ◽  
Judith A. Mack ◽  
Edward V. Maytin
Keyword(s):  
Wound Healing ◽  
Chronic Wounds ◽  
Skin Wound ◽  
Skin Wound Healing ◽  
Glucose Levels ◽  
Cytokine Levels ◽  
The Status ◽  
Perivascular Area ◽  
Induced Changes ◽  
Cutaneous Blood

Ulcers and chronic wounds are a particularly common problem in diabetics and are associated with hyperglycemia. In this targeted review, we summarize evidence suggesting that defective wound healing in diabetics is causally linked, at least in part, to hyperglycemia-induced changes in the status of hyaluronan (HA) that resides in the pericellular coat (glycocalyx) of endothelial cells of small cutaneous blood vessels. Potential mechanisms through which exposure to high glucose levels causes a loss of the glycocalyx on the endothelium and accelerates the recruitment of leukocytes, creating a proinflammatory environment, are discussed in detail. Hyperglycemia also affects other cells in the immediate perivascular area, including pericytes and smooth muscle cells, through exposure to increased cytokine levels and through glucose elevations in the interstitial fluid. Possible roles of newly recognized, cross-linked forms of HA, and interactions of a major HA receptor (CD44) with cytokine/growth factor receptors during hyperglycemia, are also discussed.

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