Plasma gelsolin promotes re-epithelialization

Wittmann, Jürgen; Dieckow, Julia; Hampel, Ulrike; Garreis, Fabian; Jacobi, Christina; Milczarek, A.; Hsieh, Kevin; Pulli, Benjamin; Chen, J. W.; Hoogeboom, Sebastian; Bräuer, Lars; Paulsen, Friedrich; Schob, Stefan; Schicht, Martin

doi:10.1038/s41598-018-31441-2

Cited by 16 publications

(21 citation statements)

References 50 publications

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“…In the present study, we have demonstrated that rhuGSN (0.375-12.5 μg/mL) increases cell viability and promotes fibroblast proliferation, leading to wound healing in 3T3-L1 cells. Our findings are consistent with previous reports demonstrating the proliferative effect of recombinant pGSN on human corneal epithelial cells and mesangial cells [34][35][36]. The rhuGSN also exhibited antioxidant property by protecting the cells from oxidative stress induced by H 2 O 2 exposure.…”

Section: Discussionsupporting

confidence: 93%

“…Interestingly, gelsolin also exhibits anti-inflammatory properties, and its ability to modulate the polymeric state of actin is pivotal for cell proliferation and final topology of cell-cell layering [46]. In an ocular surface regeneration model, recombinant plasmatic gelsolin therapy promoted wound healing by acting on the epithelial cells as well as in deeper corneal layers such as the stroma, where fibroblasts are differentiated into myofibroblasts [34]. The role of gelsolin as actin regulatory protein is well established [15,47,48].…”

Section: Discussionmentioning

confidence: 99%

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Antioxidant and Wound Healing Property of Gelsolin in 3T3-L1 Cells

Vaid

Chopra

Raut

et al. 2020

Oxidative Medicine and Cellular Longevity

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Delineation of factors which affect wound healing would be of immense value to enable on-time or early healing and reduce comorbidities associated with infections or biochemical stress like diabetes. Plasma gelsolin has been identified earlier to significantly enable injury recovery compared to placebo. This study evaluates the role of rhuGSN for its antioxidant and wound healing properties in murine fibroblasts (3T3-L1 cell line). Total antioxidant capacity of rhuGSN increased in a concentration-dependent manner (0.75-200 μg/mL). Cells pretreated with 0.375 and 0.75 μg/mL rhuGSN for 24 h exhibited a significant increase in viability in a MTT assay. Preincubation of cells with rhuGSN for 24 h followed by oxidative stress induced by exposure to H2O2 for 3 h showed cytoprotective effect. rhuGSN at 12.5 and 25 μg/mL concentration showed an enhanced cell migration after 20 h of injury in a scratch wound healing assay. The proinflammatory cytokine IL-6 levels were elevated in the culture supernatant. These results establish an effective role of rhuGSN against oxidative stress induced by H2O2 and in wound healing of 3T3-L1 fibroblast cells.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Antioxidant and Wound Healing Property of Gelsolin in 3T3-L1 Cells

Vaid

Chopra

Raut

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…Sepsis and septic shock represent very serious medical conditions that require a complex therapeutic approach and use of a spectrum of drugs assuring multidirectional biological activity. A compelling number of studies report that pGSN, apart from having actin-scavenging properties, exerts a number of effects in pathogenesis including protection against infections, implication in wound healing and re-epithelization, bone remodeling, and the stabilization of intracellular calcium concentrations [5,22]. Importantly, in mice not expressing GSN, dysfunction in inflammatory reactions, including the delayed in vivo migration of neutrophils and impaired chemotaxis was observed [23].…”

Section: Discussionmentioning

confidence: 99%

Recombinant Human Plasma Gelsolin Stimulates Phagocytosis while Diminishing Excessive Inflammatory Responses in Mice with Pseudomonas aeruginosa Sepsis

Piktel

Wnorowska

Cieśluk

et al. 2020

IJMS

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Plasma gelsolin (pGSN) is a highly conserved abundant circulating protein, characterized by diverse immunomodulatory activities including macrophage activation and the ability to neutralize pro-inflammatory molecules produced by the host and pathogen. Using a murine model of Gram-negative sepsis initiated by the peritoneal instillation of Pseudomonas aeruginosa Xen 5, we observed a decrease in the tissue uptake of IRDye®800CW 2-deoxyglucose, an indicator of inflammation, and a decrease in bacterial growth from ascitic fluid in mice treated with intravenous recombinant human plasma gelsolin (pGSN) compared to the control vehicle. Pretreatment of the murine macrophage line RAW264.7 with pGSN, followed by addition of Pseudomonas aeruginosa Xen 5, resulted in a dose-dependent increase in the proportion of macrophages with internalized bacteria. This increased uptake was less pronounced when cells were pretreated with pGSN and then centrifuged to remove unbound pGSN before addition of bacteria to macrophages. These observations suggest that recombinant plasma gelsolin can modulate the inflammatory response while at the same time augmenting host antibacterial activity.

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“…patients with diabetes. Of note, treatment with gelsolin has been observed to decrease IL-6 levels in mice (Cheng et al, 2017) and has been suggested to promote epithelial repair (Wittmann et al, 2018) . The development of therapies to stabilise the gelsolin levels could hence be of direct therapeutic value for treating COVID-19.…”

Section: Tissue Injury and Dysregulation Of Modulators Of Inflammationmentioning

confidence: 99%

“…Of note, treatment with gelsolin has been observed to decrease IL-6 levels in mice (Cheng et al, 2017) . Gelsolin treatment has been suggested to promote epithelial repair (Wittmann et al, 2018) .…”

Section: Supplementary Informationmentioning

confidence: 99%

Clinical classifiers of COVID-19 infection from novel ultra-high-throughput proteomics

Messner

Demichev

Wendisch

et al. 2020

Preprint

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The COVID-19 pandemic is an unprecedented global challenge. Highly variable in its presentation, spread and clinical outcome, novel point-of-care diagnostic classifiers are urgently required. Here, we describe a set of COVID-19 clinical classifiers discovered using a newly designed low-cost high-throughput mass spectrometry-based platform. Introducing a new sample preparation pipeline coupled with short-gradient high-flow liquid chromatography and mass spectrometry, our methodology facilitates clinical implementation and increases sample throughput and quantification precision. Providing a rapid assessment of serum or plasma samples at scale, we report 27 biomarkers that distinguish mild and severe forms of COVID-19, of which some may have potential as therapeutic targets. These proteins highlight the role of complement factors, the coagulation system, inflammation modulators as well as pro-inflammatory signalling upstream and downstream of Interleukin 6. Application of novel methodologies hence transforms proteomics from a research tool into a rapid-response, clinically actionable technology adaptable to infectious outbreaks. Highlights-A completely redesigned clinical proteomics platform increases throughput and precision while reducing costs.-27 biomarkers are differentially expressed between WHO severity grades for COVID-19.-The study highlights potential therapeutic targets that include complement factors, the coagulation system, inflammation modulators as well as pro-inflammatory signalling both upstream and downstream of interleukin 6.

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Plasma gelsolin promotes re-epithelialization

Cited by 16 publications

References 50 publications

Antioxidant and Wound Healing Property of Gelsolin in 3T3-L1 Cells

Antioxidant and Wound Healing Property of Gelsolin in 3T3-L1 Cells

Recombinant Human Plasma Gelsolin Stimulates Phagocytosis while Diminishing Excessive Inflammatory Responses in Mice with Pseudomonas aeruginosa Sepsis

Clinical classifiers of COVID-19 infection from novel ultra-high-throughput proteomics

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