scholarly journals Skin wound closure delay in metabolic syndrome correlates with SCF deficiency in keratinocytes

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Zhenping Wang ◽  
Yanhan Wang ◽  
Nicholas Bradbury ◽  
Carolina Gonzales Bravo ◽  
Bernd Schnabl ◽  
...  
Keyword(s):  
Immune Cells ◽  
Wound Repair ◽  
Molecular Mechanisms ◽  
Wound Closure ◽  
Skin Wound ◽  
Skin Cells ◽  
Transient Activation ◽  
Kit Receptor ◽  
Repair Mechanisms ◽  
Current Therapies

AbstractPoor wound closure due to diabetes, aging, stress, obesity, alcoholism, and chronic disease affects millions of people worldwide. Reasons wounds will not close are still unclear, and current therapies are limited. Although stem cell factor (SCF), a cytokine, is known to be important for wound repair, the cellular and molecular mechanisms of SCF in wound closure remain poorly understood. Here, we found that SCF expression in the epidermis is decreased in mouse models of delayed wound closure intended to mimic old age, obesity, and alcoholism. By using SCF conditionally knocked out mice, we demonstrated that keratinocytes’ autocrine production of SCF activates a transient c-kit receptor in keratinocytes. Transient activation of the c-kit receptor induces the expression of growth factors and chemokines to promote wound re-epithelialization by increasing migration of skin cells (keratinocytes and fibroblasts) and immune cells (neutrophils) to the wound bed 24–48 h post-wounding. Our results demonstrate that keratinocyte-produced SCF is essential to wound closure due to the increased recruitment of a unique combination of skin cells and immune cells in the early phase after wounding. This discovery is imperative for developing clinical strategies that might improve the body’s natural repair mechanisms for treating patients with wound-closure pathologies.

Delayed wound healing in elderly people

2009 ◽  
Vol 19 (3) ◽  
pp. 171-184 ◽  
Author(s):  
Helen A. Thomason ◽  
Matthew J. Hardman
Keyword(s):  
Inflammatory Response ◽  
Elderly People ◽  
Wound Repair ◽  
Molecular Mechanisms ◽  
Chronic Wounds ◽  
Large Body ◽  
The Elderly ◽  
Elderly Subjects ◽  
Delayed Wound Healing ◽  
Current Therapies

SummaryOur ability to heal wounds deteriorates with age, leading in many cases to a complete lack of repair and development of a chronic wound. Moreover, as the elderly population continues to grow the prevalence of non-healing chronic wounds is escalating. Cutaneous wound repair occurs through a combination of overlapping phases, including an initial inflammatory response, a proliferative phase and a final remodelling phase. In elderly subjects the inflammatory response is delayed, macrophage and fibroblast function compromised, angiogenesis reduced and re-epithelialization inhibited. Whilst a large body of historic research describes the defective processes that lead to delayed healing, only recently have the molecular mechanisms by which these defects arise begun to be elucidated. Current therapies available for treatment of chronic wounds in elderly people are surprisingly limited and generally ineffective. Thus there is an urgent need to develop new therapeutic strategies based on these recent molecular and cellular insights.

Delayed skin wound repair in proline-rich protein tyrosine kinase 2 knockout mice

2014 ◽  
Vol 306 (10) ◽  
pp. C899-C909 ◽  
Author(s):  
Aaron C. Koppel ◽  
Alexi Kiss ◽  
Anna Hindes ◽  
Carole J. Burns ◽  
Barry L. Marmer ◽  
...  
Keyword(s):  
Wound Repair ◽  
Protein Tyrosine Kinase ◽  
Wound Closure ◽  
Skin Wound ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Tyrosine Kinase 2 ◽  
Scratch Wound ◽  
Protein Tyrosine Kinase 2

Proline-rich protein tyrosine kinase 2 (Pyk2) is a member of the focal adhesion kinase family. We used Pyk2 knockout (Pyk2-KO) mice to study the role of Pyk2 in cutaneous wound repair. We report that the rate of wound closure was delayed in Pyk2-KO compared with control mice. To examine whether impaired wound healing of Pyk2-KO mice was caused by a keratinocyte cell-autonomous defect, the capacities of primary keratinocytes from Pyk2-KO and wild-type (WT) littermates to heal scratch wounds in vitro were compared. The rate of scratch wound repair was decreased in Pyk2-KO keratinocytes compared with WT cells. Moreover, cultured human epidermal keratinocytes overexpressing the dominant-negative mutant of Pyk2 failed to heal scratch wounds. Conversely, stimulation of Pyk2-dependent signaling via WT Pyk2 overexpression induced accelerated scratch wound closure and was associated with increased expression of matrix metalloproteinase (MMP)-1, MMP-9, and MMP-10. The Pyk2-stimulated increase in the rate of scratch wound repair was abolished by coexpression of the dominant-negative mutant of PKCδ and by GM-6001, a broad-spectrum inhibitor of MMP activity. These results suggest that Pyk2 is essential for skin wound reepithelialization in vivo and in vitro and that it regulates epidermal keratinocyte migration via a pathway that requires PKCδ and MMP functions.

scholarly journals Rhamm−/− fibroblasts are defective in CD44-mediated ERK1,2 motogenic signaling, leading to defective skin wound repair

2006 ◽  
Vol 175 (6) ◽  
pp. 1017-1028 ◽  
Author(s):  
Cornelia Tolg ◽  
Sara R. Hamilton ◽  
Kerry-Ann Nakrieko ◽  
Fatemeh Kooshesh ◽  
Paul Walton ◽  
...  
Keyword(s):  
Cell Surface ◽  
Wound Repair ◽  
Molecular Mechanisms ◽  
Skin Wound ◽  
Collagen Gels ◽  
Subcellular Targeting ◽  
Normal Tissues ◽  
Fibroblast Migration ◽  
Extracellular Compartment

Rhamm (receptor for hyaluronan-mediated motility) is an hyaluronan binding protein with limited expression in normal tissues and high expression in advanced cancers. To understand its physiological functions and identify the molecular mechanisms underlying these functions, we created mice with a genetic deletion of Rhamm. We show that Rhamm−/− fibroblasts fail to resurface scratch wounds >3 mm or invade hyaluronan-supplemented collagen gels in culture. We identify a requirement for Rhamm in the localization of CD44 to the cell surface, formation of CD44–ERK1,2 (extracellular-regulated kinase 1,2) complexes, and activation/subcellular targeting of ERK1,2 to the cell nucleus. We also show that cell surface Rhamm, restricted to the extracellular compartment by linking recombinant protein to beads, and expression of mutant active mitogen-activated kinase kinase 1 (Mek1) are sufficient to rescue aberrant signaling through CD44–ERK1,2 complexes in Rh−/− fibroblasts. ERK1,2 activation and fibroblast migration/differentiation is also defective during repair of Rh−/− excisional skin wounds and results in aberrant granulation tissue in vivo. These results identify Rhamm as an essential regulator of CD44–ERK1,2 fibroblast motogenic signaling required for wound repair.

scholarly journals Chitosan-Based Functional Materials for Skin Wound Repair: Mechanisms and Applications

2021 ◽  
Vol 9 ◽  
Author(s):  
Peipei Feng ◽  
Yang Luo ◽  
Chunhai Ke ◽  
Haofeng Qiu ◽  
Wei Wang ◽  
...  
Keyword(s):  
Wound Repair ◽  
Functional Materials ◽  
High Water ◽  
Skin Wound ◽  
Wound Dressings ◽  
Chemical Components ◽  
Intrinsic Nature ◽  
Repair Mechanisms ◽  
Other Substances ◽  
Polymeric Biomaterial

Skin wounds not only cause physical pain for patients but also are an economic burden for society. It is necessary to seek out an efficient approach to promote skin repair. Hydrogels are considered effective wound dressings. They possess many unique properties like biocompatibility, biodegradability, high water uptake and retention etc., so that they are promising candidate materials for wound healing. Chitosan is a polymeric biomaterial obtained by the deacetylation of chitin. With the properties of easy acquisition, antibacterial and hemostatic activity, and the ability to promote skin regeneration, hydrogel-like functional wound dressings (represented by chitosan and its derivatives) have received extensive attentions for their effectiveness and mechanisms in promoting skin wound repair. In this review, we extensively discussed the mechanisms with which chitosan-based functional materials promote hemostasis, anti-inflammation, proliferation of granulation in wound repair. We also provided the latest information about the applications of such materials in wound treatment. In addition, we summarized the methods to enhance the advantages and maintain the intrinsic nature of chitosan via incorporating other chemical components, active biomolecules and other substances into the hydrogels.

scholarly journals Cellular and Molecular Characteristics of Scarless versus Fibrotic Wound Healing

2010 ◽  
Vol 2010 ◽  
pp. 1-11 ◽  
Author(s):  
Latha Satish ◽  
Sandeep Kathju
Keyword(s):  
Wound Healing ◽  
Wound Repair ◽  
Molecular Mechanisms ◽  
Skin Wound ◽  
Molecular Characteristics ◽  
Skin Wound Healing ◽  
Cellular Events ◽  
Compare And Contrast ◽  
Adult Skin ◽  
Fetal Wound

The purpose of this paper is to compare and contrast the discrete biology differentiating fetal wound repair from its adult counterpart. Integumentary wound healing in mammalian fetuses is essentially different from wound healing in adult skin. Adult (postnatal) skin wound healing is a complex and well-orchestrated process spurred by attendant inflammation that leads to wound closure with scar formation. In contrast, fetal wound repair occurs with minimal inflammation, faster re-epithelialization, and without the accumulation of scar. Although research into scarless healing began decades ago, the critical molecular mechanisms driving the process of regenerative fetal healing remain uncertain. Understanding the molecular and cellular events during regenerative healing may provide clues that one day enable us to modulate adult wound healing and consequently reduce scarring.

Role of Resveratrol in Modulating microRNAs in Human Diseases: From Cancer to Inflammatory Disorder

2020 ◽  
Vol 28 (2) ◽  
pp. 360-376 ◽  
Author(s):  
Atefeh Amiri ◽  
Maryam Mahjoubin-Tehran ◽  
Zatollah Asemi ◽  
Alimohammad Shafiee ◽  
Sarah Hajighadimi ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Antioxidant Activities ◽  
Natural Compounds ◽  
Therapeutic Effects ◽  
Inflammatory Disorder ◽  
Inflammatory Disorders ◽  
Therapeutic Modalities ◽  
Anti Cancer ◽  
Current Therapies ◽  
Anti Inflammatory

: Cancer and inflammatory disorders are two important public health issues worldwide with significant socio.economic impacts. Despite several efforts, the current therapeutic platforms are associated with severe limitations. Therefore, developing new therapeutic strategies for the treatment of these diseases is a top priority. Besides current therapies, the utilization of natural compounds has emerged as a new horizon for the treatment of cancer and inflammatory disorders as well. Such natural compounds could be used either alone or in combination with the standard cancer therapeutic modalities such as chemotherapy, radiotherapy, and immunotherapy. Resveratrol is a polyphenolic compound that is found in grapes as well as other foods. It has been found that this medicinal agent displays a wide pharmacological spectrum, including anti-cancer, anti-inflammatory, anti-microbial, and antioxidant activities. Recently, clinical and pre-clinical studies have highlighted the anti-cancer and anti-inflammatory effects of resveratrol. Increasing evidence revealed that resveratrol exerts its therapeutic effects by targeting various cellular and molecular mechanisms. Among cellular and molecular targets that are modulated by resveratrol, microRNAs (miRNAs) have appeared as key targets. MiRNAs are short non-coding RNAs that act as epigenetic regulators. These molecules are involved in many processes that are involved in the initiation and progression of cancer and inflammatory disorders. Herein, we summarized various miRNAs that are directly/indirectly influenced by resveratrol in cancer and inflammatory disorders.

scholarly journals Overexpression of the Oral Mucosa-Specific microRNA-31 Promotes Skin Wound Closure

2019 ◽  
Vol 20 (15) ◽  
pp. 3679 ◽  
Author(s):  
Lin Chen ◽  
Alyne Simões ◽  
Zujian Chen ◽  
Yan Zhao ◽  
Xinming Wu ◽  
...  
Keyword(s):  
Wound Healing ◽  
Oral Mucosa ◽  
Wound Closure ◽  
Expression Patterns ◽  
Skin Wound ◽  
Skin Wound Healing ◽  
Specific Expression ◽  
Keratinocyte Proliferation

Wounds within the oral mucosa are known to heal more rapidly than skin wounds. Recent studies suggest that differences in the microRNAome profiles may underlie the exceptional healing that occurs in oral mucosa. Here, we test whether skin wound-healing can be accelerating by increasing the levels of oral mucosa-specific microRNAs. A panel of 57 differentially expressed high expresser microRNAs were identified based on our previously published miR-seq dataset of paired skin and oral mucosal wound-healing [Sci. Rep. (2019) 9:7160]. These microRNAs were further grouped into 5 clusters based on their expression patterns, and their differential expression was confirmed by TaqMan-based quantification of LCM-captured epithelial cells from the wound edges. Of these 5 clusters, Cluster IV (consisting of 8 microRNAs, including miR-31) is most intriguing due to its tissue-specific expression pattern and temporal changes during wound-healing. The in vitro functional assays show that ectopic transfection of miR-31 consistently enhanced keratinocyte proliferation and migration. In vivo, miR-31 mimic treatment led to a statistically significant acceleration of wound closure. Our results demonstrate that wound-healing can be enhanced in skin through the overexpression of microRNAs that are highly expressed in the privileged healing response of the oral mucosa.

scholarly journals Immune Actions on the Peripheral Nervous System in Pain

2021 ◽  
Vol 22 (3) ◽  
pp. 1448
Author(s):  
Jessica Aijia Liu ◽  
Jing Yu ◽  
Chi Wai Cheung
Keyword(s):  
Chronic Pain ◽  
Nervous System ◽  
Peripheral Nervous System ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Process Integration ◽  
Current Knowledge ◽  
Therapeutic Strategies ◽  
Lipid Mediators ◽  
Cellular Changes

Pain can be induced by tissue injuries, diseases and infections. The interactions between the peripheral nervous system (PNS) and immune system are primary actions in pain sensitizations. In response to stimuli, nociceptors release various mediators from their terminals that potently activate and recruit immune cells, whereas infiltrated immune cells further promote sensitization of nociceptors and the transition from acute to chronic pain by producing cytokines, chemokines, lipid mediators and growth factors. Immune cells not only play roles in pain production but also contribute to PNS repair and pain resolution by secreting anti-inflammatory or analgesic effectors. Here, we discuss the distinct roles of four major types of immune cells (monocyte/macrophage, neutrophil, mast cell, and T cell) acting on the PNS during pain process. Integration of this current knowledge will enhance our understanding of cellular changes and molecular mechanisms underlying pain pathogenies, providing insights for developing new therapeutic strategies.

scholarly journals Is a diluted seawater-based solution safe and effective on human nasal epithelium?

2021 ◽  
Author(s):  
Song Huang ◽  
Samuel Constant ◽  
Barbara De Servi ◽  
Marisa Meloni ◽  
Amina Saaid ◽  
...  
Keyword(s):  
Wound Repair ◽  
Wound Closure ◽  
Isotonic Saline ◽  
Nasal Epithelium ◽  
Mucin Secretion ◽  
Nasal Irrigation ◽  
Tissue Integrity ◽  
Human Nasal Epithelium ◽  
Pre Treatment

Abstract Purpose Nasal irrigation is an effective method for alleviating several nasal symptoms and regular seawater-based nasal irrigation is useful for maintaining nasal hygiene which is essential for appropriate functioning of the nose and for preventing airborne particles including some pollutants, pathogens, and allergens from moving further in the respiratory system. However, safety studies on seawater-based nasal irrigation are scarce. In this study, the safety and efficacy of a diluted isotonic seawater solution (Stérimar Nasal Hygiene, SNH) in maintaining nasal homeostasis were evaluated in vitro. Methods Safety was assessed by measuring tissue integrity via transepithelial electrical resistance (TEER). Efficacy was measured by mucociliary clearance (MCC), mucin secretion, and tissue re-epithelization (wound repair) assays. All assays were performed using a 3D reconstituted human nasal epithelium model. Results In SNH-treated tissues, TEER values were statistically significantly lower than the untreated tissues; however, the values were above the tissue integrity limit. SNH treatment significantly increased MCC (88 vs. 36 µm/s, p < 0.001) and mucin secretion (1717 vs. 1280 µg/ml, p < 0.001) as compared to untreated cultures. Faster wound closure profile was noted upon pre-SNH treatment as compared to classical isotonic saline solution pre-treatment (90.5 vs. 50.7% wound closure 22 h after wound generation). Conclusion SNH did not compromise the integrity of the nasal epithelium in vitro. Furthermore, SNH was effective for removal of foreign particles through MCC increase and for enhancing wound repair on nasal mucosa.

scholarly journals A pulsatile release platform based on photo-induced imine-crosslinking hydrogel promotes scarless wound healing

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jian Zhang ◽  
Yongjun Zheng ◽  
Jimmy Lee ◽  
Jieyu Hua ◽  
Shilong Li ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Repair ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Skin Wound ◽  
Large Animal ◽  
Skin Wounds ◽  
Tgfβ Signaling ◽  
Pulsatile Release ◽  
Ecm Extracellular Matrix

AbstractEffective healing of skin wounds is essential for our survival. Although skin has strong regenerative potential, dysfunctional and disfiguring scars can result from aberrant wound repair. Skin scarring involves excessive deposition and misalignment of ECM (extracellular matrix), increased cellularity, and chronic inflammation. Transforming growth factor-β (TGFβ) signaling exerts pleiotropic effects on wound healing by regulating cell proliferation, migration, ECM production, and the immune response. Although blocking TGFβ signaling can reduce tissue fibrosis and scarring, systemic inhibition of TGFβ can lead to significant side effects and inhibit wound re-epithelization. In this study, we develop a wound dressing material based on an integrated photo-crosslinking strategy and a microcapsule platform with pulsatile release of TGF-β inhibitor to achieve spatiotemporal specificity for skin wounds. The material enhances skin wound closure while effectively suppressing scar formation in murine skin wounds and large animal preclinical models. Our study presents a strategy for scarless wound repair.

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