scholarly journals Myeloid-derived growth factor regulates neutrophil motility in interstitial tissue damage

2021 ◽  
Vol 220 (8) ◽  
Author(s):  
Ruth A. Houseright ◽  
Veronika Miskolci ◽  
Oscar Mulvaney ◽  
Valeriu Bortnov ◽  
Deane F. Mosher ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Host Defense ◽  
Tissue Damage ◽  
Tissue Repair ◽  
Interstitial Tissue ◽  
Paracrine Factor ◽  
Reverse Migration ◽  
Zebrafish Larvae ◽  
Inflammation Resolution

Neutrophil recruitment to tissue damage is essential for host defense but can also impede tissue repair. The cues that differentially regulate neutrophil responses to tissue damage and infection remain unclear. Here, we report that the paracrine factor myeloid-derived growth factor (MYDGF) is induced by tissue damage and regulates neutrophil motility to damaged, but not infected, tissues in zebrafish larvae. Depletion of MYDGF impairs wound healing, and this phenotype is rescued by depleting neutrophils. Live imaging and photoconversion reveal impaired neutrophil reverse migration and inflammation resolution in mydgf mutants. We found that persistent neutrophil inflammation in tissues of mydgf mutants was dependent on the HIF-1α pathway. Taken together, our data suggest that MYDGF is a damage signal that regulates neutrophil interstitial motility and inflammation through a HIF-1α pathway in response to tissue damage.

scholarly journals The CXCL12/CXCR4 signalling axis retains neutrophils at inflammatory sites in zebrafish

2019 ◽  
Author(s):  
Hannah M. Isles ◽  
Kimberly Herman ◽  
Anne L. Robertson ◽  
Catherine A. Loynes ◽  
Lynne R. Prince ◽  
...  
Keyword(s):  
Inflammatory Disease ◽  
Tissue Damage ◽  
Tissue Injury ◽  
Transgenic Zebrafish ◽  
Sequencing Data ◽  
Cxcr4 Antagonist ◽  
Reverse Migration ◽  
Zebrafish Larvae ◽  
Inflammation Resolution

AbstractThe inappropriate retention of neutrophils in the lung is a major driver of the excessive tissue damage characteristic of respiratory inflammatory diseases including COPD, ARDS and cystic fibrosis. The molecular programmes which orchestrate neutrophil recruitment to inflammatory sites through chemotactic guidance have been well studied. However, how neutrophil sensitivity to these cues is modulated during inflammation resolution is not understood. The identification of neutrophil reverse migration as a mechanism of inflammation resolution and the ability to modulate this therapeutically has identified a new target to treat inflammatory disease. Here we investigate the role of the CXCL12/CXCR4 signalling axis in modulating neutrophil retention at inflammatory sites. We used an in vivo tissue injury model to study inflammation using transgenic zebrafish larvae. Expression of cxcl12a and cxcr4b during the tissue damage response was assessed using in situ hybridisation and analysis of RNA sequencing data. CRISPR/Cas9 was used to knockdown cxcl12a and cxcr4b in zebrafish larvae. The CXCR4 antagonist AMD3100 was used to block the Cxcl12/Cxcr4 signalling axis pharmacologically. We identified that cxcr4b and cxcl12a are expressed at the wound site in zebrafish larvae during the inflammatory response. Following tail-fin transection, removal of neutrophils from inflammatory sites is significantly increased in cxcr4b and cxcl12a CRISPR knockdown larvae. Pharmacological inhibition of the Cxcl12/Cxcr4 signalling axis accelerates inflammation resolution, an effect caused by an increase in neutrophil reverse migration. The findings of this study suggest that CXCR4/CXCL12 signalling may play an important role in neutrophil retention at inflammatory sites, identifying a potential new target for the therapeutic removal of neutrophils from the lung in chronic inflammatory disease.

scholarly journals In vivo incisional wound healing augmented by platelet-derived growth factor and recombinant c-sis gene homodimeric proteins.

1988 ◽  
Vol 167 (3) ◽  
pp. 974-987 ◽  
Author(s):  
G F Pierce ◽  
T A Mustoe ◽  
R M Senior ◽  
J Reed ◽  
G L Griffin ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Tissue Repair ◽  
Inflammatory Cells ◽  
Cell Types ◽  
Platelet Derived Growth Factor ◽  
Inflammatory Cell Infiltrate ◽  
In Vitro Tests

Human platelet-derived growth factor (hPDGF) is likely to be important in stimulating tissue repair, based upon its in vivo chemotactic and stimulatory activities for inflammatory cells and fibroblasts and upon the presence of PDGF and related proteins in platelets, macrophages, and activated fibroblasts, cell types that make up the milieu of the healing wound. Recombinant human c-sis (rPDGF-B), homodimers of the B chain of PDGF, were compared with hPDGF in vitro. rPDGF-B was immunologically similar to hPDGF and, at identical concentrations, similar to hPDGF in stimulating fibroblast mitogenesis and chemotaxis of polymorphonuclear leukocytes, monocytes, and fibroblasts. Purified hPDGF and rPDGF-B were also tested in vivo for potency in a model of tissue repair using a linear incision wound through rat dermis. A single application of hPDGF or rPDGF-B (2-20 micrograms/wound) in a slow release vehicle at the time of wounding resulted in a dose-dependent, statistically highly significant increase of breaking strength of treated wounds. Wound healing in animals treated with rPDGF-B was 170% stronger and accelerated by 2 d during the first week over control wounds and by 4-6 d over the next 2 wk. Histologic evaluation of growth factor-treated wounds correlated the in vitro chemotactic activity and the accelerated healing of wounds with a striking inflammatory cell infiltrate early after wounding, markedly increased formation of granulation tissue by 4-d, and increased fibrosis by 14 d in comparison to control wounds. The results thus demonstrate that rPDGF-B is fully active in in vitro tests of mitogenesis and chemotaxis and, for the first time, demonstrate directly that PDGF significantly advances wound healing in incisional wounds of experimental animals.

scholarly journals Development of stabilized dual growth factor-loaded hyaluronate collagen dressing matrix

2021 ◽  
Vol 12 ◽  
pp. 204173142199975
Author(s):  
Jihyun Kim ◽  
Kyoung-Mi Lee ◽  
Seung Hwan Han ◽  
Eun Ae Ko ◽  
Dong Suk Yoon ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Type I ◽  
Diabetic Mice ◽  
Patients With Diabetes ◽  
Diabetic Wound Healing ◽  
Epidermal Growth ◽  
Wound Healing Effect ◽  
Growth Factor Production

Patients with diabetes experience impaired growth factor production such as epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF), and they are reportedly involved in wound healing processes. Here, we report dual growth factor-loaded hyaluronate collagen dressing (Dual-HCD) matrix, using different ratios of the concentration of stabilized growth factors—stabilized-EGF (S-EGF) and stabilized-bFGF (S-bFGF). At first, the optimal concentration ratio of S-EGF to S-bFGF in the Dual-HCD matrix is determined to be 1:2 in type I diabetic mice. This Dual-HCD matrix does not cause cytotoxicity and can be used in vivo. The wound-healing effect of this matrix is confirmed in type II diabetic mice. Dual HCD enhances angiogenesis which promotes wound healing and thus, it shows a significantly greater synergistic effect than the HCD matrix loaded with a single growth factor. Overall, we conclude that the Dual-HCD matrix represents an effective therapeutic agent for impaired diabetic wound healing.

scholarly journals Sustained Release of Insulin-Like Growth Factor-1 from Bombyx mori L. Silk Fibroin Delivery for Diabetic Wound Therapy

2021 ◽  
Vol 22 (12) ◽  
pp. 6267
Author(s):  
Meng-Jin Lin ◽  
Mei-Chun Lu ◽  
Hwan-You Chang
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Sustained Release ◽  
Silk Fibroin ◽  
Granulation Tissue ◽  
Release Rate ◽  
Insulin Like Growth Factor ◽  
Diabetic Wound ◽  
Diabetic Mice ◽  
Wound Therapy

The goals of this study are to develop a high purity patented silk fibroin (SF) film and test its suitability to be used as a slow-release delivery for insulin-like growth factor-1 (IGF-1). The release rate of the SF film delivering IGF-1 followed zero-order kinetics as determined via the Ritger and Peppas equation. The release rate constant was identified as 0.11, 0.23, and 0.09% h−1 at 37 °C for SF films loaded with 0.65, 6.5, and 65 pmol IGF-1, respectively. More importantly, the IGF-1 activity was preserved for more than 30 days when complexed with the SF film. We show that the IGF-1-loaded SF films significantly accelerated wound healing in vitro (BALB/3T3) and in vivo (diabetic mice), compared with wounds treated with free IGF-1 and an IGF-1-loaded hydrocolloid dressing. This was evidenced by a six-fold increase in the granulation tissue area in the IGF-1-loaded SF film treatment group compared to that of the PBS control group. Western blotting analysis also demonstrated that IGF-1 receptor (IGF1R) phosphorylation in diabetic wounds increased more significantly in the IGF-1-loaded SF films group than in other experimental groups. Our results suggest that IGF-1 sustained release from SF films promotes wound healing through continuously activating the IGF1R pathway, leading to the enhancement of both wound re-epithelialization and granulation tissue formation in diabetic mice. Collectively, these data indicate that SF films have considerable potential to be used as a wound dressing material for long-term IGF-1 delivery for diabetic wound therapy.

Controlled release of KGF-2 for regulation of wound healing by KGF-2 complexed with “lotus seedpod surface-like” porous microsphere

2021 ◽  
Author(s):  
Hao Pan ◽  
Changcan Shi ◽  
Rongshuai Yang ◽  
Guanghui Xi ◽  
Chao Lu ◽  
...  
Keyword(s):  
Wound Healing ◽  
Controlled Release ◽  
Growth Factor ◽  
Normal Tissue ◽  
Keratinocyte Growth Factor ◽  
Tissue Structure ◽  
Effective Strategy ◽  
Proliferation And Differentiation ◽  
Porous Microsphere ◽  
Lotus Seedpod

Keratinocyte growth factor-2 (KGF-2) plays a remarkable role in maintaining normal tissue structure and promoting wound healing by regulation the proliferation and differentiation of keratinocyte. As an effective strategy, KGF-2...

scholarly journals Infarct in the Heart: What’s MMP-9 Got to Do with It?

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 491
Author(s):  
Mediha Becirovic-Agic ◽  
Upendra Chalise ◽  
Michael J. Daseke ◽  
Shelby Konfrst ◽  
Jeffrey D. Salomon ◽  
...  
Keyword(s):  
Wound Healing ◽  
Cardiac Repair ◽  
Dual Effect ◽  
Strong Connection ◽  
The Past ◽  
Left Ventricle Remodeling ◽  
Inflammation Resolution ◽  
Metalloproteinase 9 ◽  
Cell Transition

Over the past three decades, numerous studies have shown a strong connection between matrix metalloproteinase 9 (MMP-9) levels and myocardial infarction (MI) mortality and left ventricle remodeling and dysfunction. Despite this fact, clinical trials using MMP-9 inhibitors have been disappointing. This review focuses on the roles of MMP-9 in MI wound healing. Infiltrating leukocytes, cardiomyocytes, fibroblasts, and endothelial cells secrete MMP-9 during all phases of cardiac repair. MMP-9 both exacerbates the inflammatory response and aids in inflammation resolution by stimulating the pro-inflammatory to reparative cell transition. In addition, MMP-9 has a dual effect on neovascularization and prevents an overly stiff scar. Here, we review the complex role of MMP-9 in cardiac wound healing, and highlight the importance of targeting MMP-9 only for its detrimental actions. Therefore, delineating signaling pathways downstream of MMP-9 is critical.

scholarly journals Redox and Src family kinase signaling control leukocyte wound attraction and neutrophil reverse migration

2014 ◽  
Vol 207 (5) ◽  
pp. 589-598 ◽  
Author(s):  
Sebastien Tauzin ◽  
Taylor W. Starnes ◽  
Francisco Barros Becker ◽  
Pui-ying Lam ◽  
Anna Huttenlocher
Keyword(s):  
Tissue Regeneration ◽  
Tissue Damage ◽  
Redox Signaling ◽  
Kinase Signaling ◽  
Src Family Kinase ◽  
Reverse Migration ◽  
Early Recruitment

Tissue damage induces early recruitment of neutrophils through redox-regulated Src family kinase (SFK) signaling in neutrophils. Redox-SFK signaling in epithelium is also necessary for wound resolution and tissue regeneration. How neutrophil-mediated inflammation resolves remains unclear. In this paper, we studied the interactions between macrophages and neutrophils in response to tissue damage in zebrafish and found that macrophages contact neutrophils and induce resolution via neutrophil reverse migration. We found that redox-SFK signaling through p22phox and Yes-related kinase is necessary for macrophage wound attraction and the subsequent reverse migration of neutrophils. Importantly, macrophage-specific reconstitution of p22phox revealed that macrophage redox signaling is necessary for neutrophil reverse migration. Thus, redox-SFK signaling in adjacent tissues is essential for coordinated leukocyte wound attraction and repulsion through pathways that involve contact-mediated guidance.

In vitro and in vivo Effect of Platelet-Rich Plasma-Based Autologous Topical Serum on Cutaneous Wound Healing

2021 ◽  
pp. 1-13
Author(s):  
Eduardo Anitua ◽  
Victoria Muñoz ◽  
Libe Aspe ◽  
Roberto Tierno ◽  
Adrian García-Salvador ◽  
...  
Keyword(s):  
Wound Healing ◽  
Tissue Damage ◽  
Collagen Synthesis ◽  
Dermal Fibroblast ◽  
Platelet Rich Plasma ◽  
Cell Activity ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound ◽  
Fibroblast Migration ◽  
Edge Contraction

<b><i>Introduction:</i></b> Skin injury and wound healing is an inevitable event during lifetime. However, several complications may hamper the regeneration of the cutaneous tissue and lead to a chronic profile that prolongs patient recovery. Platelet-rich plasma is rising as an effective and safe alternative to the management of wounds. However, this technology presents some limitations such as the need for repeated blood extractions and health-care interventions. <b><i>Objective:</i></b> The aim of this study was to assess the use of an endogenous and storable topical serum (ES) derived from plasma rich in growth factors promoting wound healing, and to obtain preliminary data regarding its clinical and experimental effect over ulcerated skin models and patient care. <b><i>Methods:</i></b> Human dermal fibroblast and 3D organotypic ulcerated skin models were used to assess ES over the main mechanisms of wound healing including cell migration, edge contraction, collagen synthesis, tissue damage, extracellular matrix remodeling, cell death, metabolic activity, and histomorphometry analysis. Additionally, 4 patients suffering from skin wounds were treated and clinically assessed. <b><i>Results:</i></b> ES promoted dermal fibroblast migration, wound edge contraction, and collagen synthesis. When topically applied, ES increased collagen and elastin deposition and reduced tissue damage. The interstitial edema, structural integrity, and cell activity were also maintained, and apoptotic levels were reduced. Patients suffering from hard-to-heal wounds of different etiologies were treated with ES, and the ulcers healed completely within few weeks with no reported adverse events. <b><i>Conclusion:</i></b> This preliminary study suggests that ES might promote cutaneous wound healing and may be useful for accelerating the re-epithelization of skin ulcers.

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