Thioredoxin-1 augments wound healing and promote angiogenesis in a murine ischemic full-thickness wound model

Saad, Ibnalwalid; Fournier, Craig; Wilson, Rickesha; Lakshmanan, Rajesh; Selvaraju, Vaithinathan; Thirunavukkarasu, Mahesh; Palesty, J. Alexander; McFadden, David W.; Maulik, Nilanjana

doi:10.1016/j.surg.2018.05.045

Cited by 11 publications

(5 citation statements)

References 29 publications

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“…Shixiang plaster is a traditional Chinese medicine that contains calamine, frankincense, Halloysitum rubrum , calcined bone, and borneol, which could have beneficial effects on healing and tissue repair [15]. Previous studies have shown that angiogenesis is the most direct effector for the healing of wounds or ulcers [27,28]. The findings from the present study showed that treatment with both aminoguanidine, a hydrazine derivative that inhibits the formation of advanced glycosylation end products (AGEs), and shixiang plaster treatment significantly increased angiogenesis at day 7 and day 14 post-surgery, which was a finding supported by previous studies [13,29].…”

Section: Discussionmentioning

confidence: 99%

Shixiang Plaster, a Traditional Chinese Medicine, Promotes Healing in a Rat Model of Diabetic Ulcer Through the receptor for Advanced Glycation End Products (RAGE)/Nuclear Factor kappa B (NF-κB) and Vascular Endothelial Growth Factor (VEGF)/Vascular Cell Adhesion Molecule-1 (VCAM-1)/Endothelial Nitric Oxide Synthase (eNOS) Signaling Pathways

Ling

Zeng

et al. 2019

Med Sci Monit

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Background: Shixiang plaster is a traditional Chinese medicine has been used to treat chronic ulcers, including diabetic ulcers. Aminoguanidine is a hydrazine derivative that inhibits the formation of advanced glycosylation end products (AGEs). This study aimed to investigate the effects of shixiang plaster and aminoguanidine on wound healing in the streptozotocin-induced rat model of diabetes and the molecular mechanisms involved. Material/Methods: Sprague-Dawley rats treated with intraperitoneal streptozotocin and given surgical wounds were divided into the untreated chronic ulcer group (n=10), the aminoguanidine group (n=10), the shixiang plaster group (n=10), and the control group with sham surgery (n=10). Granulation tissue samples underwent light microscopy to evaluate angiogenesis and immunohistochemistry to identify AGE, vascular endothelial growth factor (VEGF), and CD34 expression. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot measured mRNA and protein expression of receptor for advanced glycation end products (RAGE), vascular cell adhesion molecule-1 (VCAM-1), nuclear factor kappa B (NF-kB) and endothelial nitric oxide synthase (eNOS). Results: The shixiang plaster group showed a significant increase in angiogenesis in ulcer granulation tissue, significantly reduced expression of AGEs and increased expression of VEGF and CD34 expression in granulation tissue compared with the untreated chronic ulcer group (p<0.05). The shixiang plaster group showed significantly down-regulated expression of RAGE and VCAM-1 compared with the untreated chronic ulcer group (p<0.05). Shixiang plaster promoted angiogenesis by activating the NF-kB p65 associated pathway and eNOS activation. Conclusions: Shixiang plaster promoted healing in a rat model of diabetic ulcer through the RAGE/NF-kB and VEGF/VCAM-1/eNOS signaling pathways.

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Section: Discussionmentioning

confidence: 99%

Shixiang Plaster, a Traditional Chinese Medicine, Promotes Healing in a Rat Model of Diabetic Ulcer Through the receptor for Advanced Glycation End Products (RAGE)/Nuclear Factor kappa B (NF-κB) and Vascular Endothelial Growth Factor (VEGF)/Vascular Cell Adhesion Molecule-1 (VCAM-1)/Endothelial Nitric Oxide Synthase (eNOS) Signaling Pathways

Ling

Zeng

et al. 2019

Med Sci Monit

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“…Here, CAP treatment leads to a local decrease of Trx1. Since Trx1 in general is considered beneficial for wound healing [39], it would here be intriguing to see if CAP-induced local loss of Trx1 indeed leads to a Trx1 secretion in this model and in vivo, therefore increasing systemically available Trx1 to counteract local oxidative dysregulation found in epidermal erosions in pemphigus.…”

Section: Discussionmentioning

confidence: 96%

Redox Enzymes of the Thioredoxin Family as Potential and Novel Markers in Pemphigus

Sliwiak

Folwarczny

Didona

et al. 2021

Oxidative Medicine and Cellular Longevity

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Pemphigus vulgaris (PV) is a severe autoimmune blistering disease affecting both skin and mucous membranes. Its pathogenesis is related to IgG autoantibodies primarily targeting the cellular adhesion protein desmoglein (Dsg) 3, one of the major desmosome components. Impaired redox regulation is considered a major player in the pathogenesis of autoimmune diseases such as pemphigus by enhancing inflammation and breakdown of immunological tolerance by structural protein modifications. Despite many recent advances, local and systemic redox profiles that characterize the immune response in pemphigus are virtually unknown but potentially crucial in further advancing our understanding of redox-dependent modifications that eventually lead to clinical manifestation. Here, we have analyzed the individual expression pattern of four major redox enzymes that are members of the thioredoxin (Trx) fold superfamily (peroxiredoxins (Prxs) 1 and 4, glutaredoxin (Grx) 2, and Trx1) in serum and PBMCs as well as their distribution in the skin of pemphigus patients compared to healthy controls. We show that in groups of five pemphigus patients, Prx1 is upregulated in both serum and PBMCs, while its epithelial distribution remains within the spinous epithelial layer. Expression of Grx2 and Prx4 is both reduced in serum and PBMCs, while their distinct and similar expression in the skin changes from an even distribution throughout the basal layer (healthy) to ubiquitous nuclear localization in pemphigus patients. In PV patients, Trx1 is secreted into serum, and cellular distribution appears membrane-bound and cytosolic compared to healthy controls. We furthermore showed that a 3D ex vivo human skin model can indeed be used to reproduce similar changes in the protein levels and distribution of redox enzymes by application of cold atmospheric plasma. Deciphering the relationship between redox enzyme expression and autoimmunity in the context of pemphigus could be critical in elucidating key pathogenic mechanisms and developing novel interventions for clinical management.

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“…Aside from elastin, the only other gene consistently regulated by PBMCsec in all three scRNAseq experimental approaches was TXNIP (Thioredoxin interacting protein). TXNIP is critically involved in the regulation of reactive oxygen species (ROS) and cellular oxidative stress [77] and was shown to contribute to disturbed wound healing under ischemic conditions [78]. With regard to scar formation, TXNIP was shown to be elevated in a murine model of pulmonary fibrosis, and the inhibition of TXNIP in this model led to the reduction in ROS and myoFB differentiation [79].…”

Section: Discussionmentioning

confidence: 99%

The Secretome of Irradiated Peripheral Mononuclear Cells Attenuates Hypertrophic Skin Scarring

et al. 2023

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Hypertrophic scars can cause pain, movement restrictions, and reduction in the quality of life. Despite numerous options to treat hypertrophic scarring, efficient therapies are still scarce, and cellular mechanisms are not well understood. Factors secreted by peripheral blood mononuclear cells (PBMCsec) have been previously described for their beneficial effects on tissue regeneration. In this study, we investigated the effects of PBMCsec on skin scarring in mouse models and human scar explant cultures at single-cell resolution (scRNAseq). Mouse wounds and scars, and human mature scars were treated with PBMCsec intradermally and topically. The topical and intradermal application of PBMCsec regulated the expression of various genes involved in pro-fibrotic processes and tissue remodeling. We identified elastin as a common linchpin of anti-fibrotic action in both mouse and human scars. In vitro, we found that PBMCsec prevents TGFβ-mediated myofibroblast differentiation and attenuates abundant elastin expression with non-canonical signaling inhibition. Furthermore, the TGFβ-induced breakdown of elastic fibers was strongly inhibited by the addition of PBMCsec. In conclusion, we conducted an extensive study with multiple experimental approaches and ample scRNAseq data demonstrating the anti-fibrotic effect of PBMCsec on cutaneous scars in mouse and human experimental settings. These findings point at PBMCsec as a novel therapeutic option to treat skin scarring.

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Thioredoxin-1 augments wound healing and promote angiogenesis in a murine ischemic full-thickness wound model

Cited by 11 publications

References 29 publications

Redox Enzymes of the Thioredoxin Family as Potential and Novel Markers in Pemphigus

The Secretome of Irradiated Peripheral Mononuclear Cells Attenuates Hypertrophic Skin Scarring

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