scholarly journals Schwann cells contribute to keloid formation

2021 ◽  
Author(s):  
Martin Direder ◽  
Tamara Weiss ◽  
Dragan Copic ◽  
Vera Vorstandlechner ◽  
Maria Laggner ◽  
...  
Keyword(s):  
Schwann Cells ◽  
Normal Skin ◽  
Scar Tissue ◽  
Functional Impairments ◽  
Novel Treatment ◽  
M2 Polarization ◽  
Keloid Formation ◽  
Hypertrophic Scar Tissue ◽  
Schwann Cell Differentiation ◽  
Abundant Population

Keloids are disfiguring, hypertrophic scars with yet poorly understood pathomechanisms, which could lead to severe functional impairments. Here we analyzed the characteristics of keloidal cells by single cell sequencing and discovered the presence of an abundant population of Schwann cells that persisted in the hypertrophic scar tissue after wound healing. In contrast to normal skin, keloidal Schwann cells possess a repair-like phenotype and high cellular plasticity. Our data support the hypothesis that keloidal Schwann cells contribute to the formation of the extracellular matrix and are able to affect M2 polarization of macrophages. Indeed, we show that macrophages in keloids predominantly display a M2 polarization and produce factors that inhibit Schwann cell differentiation. Our data suggest a contribution of this cross-talk to the continuous expansion of keloids, and that targeting Schwann cells might represent an interesting novel treatment option for keloids.

scholarly journals The Polygenic Map of Keloid Fibroblasts Reveals Fibrosis-Associated Gene Alterations in Inflammation and Immune Responses

2022 ◽  
Vol 12 ◽  
Author(s):  
Yang Li ◽  
Min Li ◽  
Caijie Qu ◽  
Yongxi Li ◽  
Zhanli Tang ◽  
...  
Keyword(s):  
T Cells ◽  
Signaling Pathways ◽  
Protein Interactions ◽  
Immune Cell ◽  
Normal Skin ◽  
Cell Activity ◽  
Scar Tissue ◽  
Gene Expression Omnibus ◽  
Genomic Expression ◽  
Keloid Formation

Due to many inconsistencies in differentially expressed genes (DEGs) related to genomic expression changes during keloid formation and a lack of satisfactory prevention and treatment methods for this disease, the critical biomarkers related to inflammation and the immune response affecting keloid formation should be systematically clarified. Normal skin/keloid scar tissue-derived fibroblast genome expression data sets were obtained from the Gene Expression Omnibus (GEO) and ArrayExpress databases. Hub genes have a high degree of connectivity and gene function aggregation in the integration network. The hub DEGs were screened by gene-related protein–protein interactions (PPIs), and their biological processes and signaling pathways were annotated to identify critical biomarkers. Finally, eighty-one hub DEGs were selected for further analysis, and some noteworthy signaling pathways and genes were found to be closely related to keloid fibrosis. For example, IL17RA is involved in IL-17 signal transduction, TIMP2 and MMP14 activate extracellular matrix metalloproteinases, and TNC, ITGB2, and ITGA4 interact with cell surface integrins. Furthermore, changes in local immune cell activity in keloid tissue were detected by DEG expression, immune cell infiltration, and mass CyTOF analyses. The results showed that CD4+ T cells, CD8+ T cells and NK cells were abnormal in keloid tissue compared with normal skin tissue. These findings not only support the key roles of fibrosis-related pathways, immune cells and critical genes in the pathogenesis of keloids but also expand our understanding of targets that may be useful for the treatment of fibrotic diseases.

scholarly journals iTRAQ-based proteomic profiling reveals different protein expression between normal skin and hypertrophic scar tissue

2015 ◽  
Vol 3 ◽  
pp. 1-8 ◽  
Author(s):  
Jianglin Tan ◽  
Weifeng He ◽  
Gaoxing Luo ◽  
Jun Wu
Keyword(s):  
Hypertrophic Scar ◽  
Normal Skin ◽  
Scar Tissue ◽  
Proteomic Profiling ◽  
Absolute Quantitation ◽  
Burn Care ◽  
Surgical Methods ◽  
Differential Proteins ◽  
Isobaric Tags ◽  
Hypertrophic Scar Tissue

Abstract Background A hypertrophic scar is a unique fibrotic disease that only exists in humans. Despite advances in burn care and rehabilitation, as well as progress in the management during these decades, the hypertrophic scar remains hard to cure following surgical methods and drugs for treatment. In this study, we are looking forward to finding the multitude of possible traumatic mechanisms and the underlying molecular signal ways in the formation of the hypertrophic scar. Methods We used isobaric tags for relative and absolute quantitation (iTRAQ) labeling technology, followed by high-throughput 2D LC-MS/MS, to determine relative quantitative differential proteins between the hypertrophic scar and normal skin tissue. Results A total of 3166 proteins were identified with a high confidence (≥95 % confidence). And, a total of 89 proteins were identified as the differential proteins between the hypertrophic scar and normal skin, among which 41 proteins were up-regulated and 48 proteins were down-regulated in the hypertrophic scar. GO-Analysis indicated the up-regulated proteins were involved in extracellular matrix, whereas the down-regulated proteins were involved in dynamic junction and structural molecule activity. Conclusions In our study, we demonstrate 89 proteins present differently in the hypertrophic scar compared to normal skin by iTRAQ technology, which might indicate the pathologic process of hypertrophic scar formation and guide us to propose new strategies against the hypertrophic scar.

NON-LINEAR SPECTRAL IMAGING MICROSCOPY STUDIES OF HUMAN HYPERTROPHIC SCAR

2009 ◽  
Vol 02 (01) ◽  
pp. 61-66 ◽  
Author(s):  
KECHENG LU ◽  
SHUANGMU ZHUO ◽  
ZHIBIN HONG ◽  
GUANNAN CHEN ◽  
XINGSHAN JIANG ◽  
...  
Keyword(s):  
Hypertrophic Scar ◽  
Normal Skin ◽  
Spectral Characteristics ◽  
Morphological Structure ◽  
Spectral Imaging ◽  
Scar Tissue ◽  
Elastic Fibers ◽  
Non Linear ◽  
Hypertrophic Scar Tissue ◽  
Skin Scar

Skin scar is unique to humans, the major significant negative outcome sustained after thermal injuries, traumatic injuries, and surgical procedures. Hypertrophic scar in human skin is investigated using non-linear spectral imaging microscopy. The high contrast images and spectroscopic intensities of collagen and elastic fibers extracted from the spectral imaging of normal skin tissue, and the normal skin near and far away from the hypertrophic scar tissues in a 10-year-old patient case are obtained. The results show that there are apparent differences in the morphological structure and spectral characteristics of collagen and elastic fibers when comparing the normal skin with the hypertrophic scar tissue. These differences can be good indicators to differentiate the normal skin and hypertrophic scar tissue and demonstrate that non-linear spectral imaging microscopy has potential to noninvasively investigate the pathophysiology of human hypertrophic scar.

scholarly journals Laminin γ1 is critical for Schwann cell differentiation, axon myelination, and regeneration in the peripheral nerve

2003 ◽  
Vol 163 (4) ◽  
pp. 889-899 ◽  
Author(s):  
Zu-Lin Chen ◽  
Sidney Strickland
Keyword(s):  
Schwann Cells ◽  
Peripheral Nerves ◽  
Matrix Proteins ◽  
Myelin Proteins ◽  
Sciatic Nerve Crush ◽  
Similar Reduction ◽  
Nerve Crush ◽  
And Function ◽  
Schwann Cell Differentiation

Laminins are heterotrimeric extracellular matrix proteins that regulate cell viability and function. Laminin-2, composed of α2, β1, and γ1 chains, is a major matrix component of the peripheral nervous system (PNS). To investigate the role of laminin in the PNS, we used the Cre–loxP system to disrupt the laminin γ1 gene in Schwann cells. These mice have dramatically reduced expression of laminin γ1 in Schwann cells, which results in a similar reduction in laminin α2 and β1 chains. These mice exhibit motor defects which lead to hind leg paralysis and tremor. During development, Schwann cells that lack laminin γ1 were present in peripheral nerves, and proliferated and underwent apoptosis similar to control mice. However, they were unable to differentiate and synthesize myelin proteins, and therefore unable to sort and myelinate axons. In mutant mice, after sciatic nerve crush, the axons showed impaired regeneration. These experiments demonstrate that laminin is an essential component for axon myelination and regeneration in the PNS.

scholarly journals Loureirin B Inhibits Hypertrophic Scar Formation via Inhibition of the TGF-β1-ERK/JNK Pathway

2015 ◽  
Vol 37 (2) ◽  
pp. 666-676 ◽  
Author(s):  
Ting He ◽  
Xiaozhi Bai ◽  
Longlong Yang ◽  
Lei Fan ◽  
Yan Li ◽  
...  
Keyword(s):  
Hypertrophic Scar ◽  
Ex Vivo ◽  
Scar Tissue ◽  
Scar Formation ◽  
Jnk Pathway ◽  
Protein Levels ◽  
Mapk Inhibitors ◽  
Hypertrophic Scar Tissue ◽  
Loureirin B ◽  
Tgf Β1

Background/Aims: Our previous study confirmed that Loureirin B (LB) can inhibit hypertrophic scar formation. However, the mechanism of LB-mediated inhibition of scar formation is still unknown. Methods: Immunohistochemistry was used to detect expression of Col1, FN and TGF-β1 in skin and scar tissue. Fibroblasts were stimulated with TGF-β1 to mimic scar formation. LB or MAPK inhibitors were used to study the pathways involved in the process. Western blotting was used to evaluate the expression of p-JNK, p-ERK, p-p38, Col1 and FN. The contractile capacity of fibroblasts was evaluated using a gel contraction assay. Tissues were cultured ex vivo with LB to further investigate the participation of ERK and JNK in the LB-mediated inhibition of scar formation. Results: FN and Col1 were up regulated in hypertrophic scars. LB down regulated p-ERK and p-JNK in TGF-β1-stimulated fibroblasts, while levels of phosphorylated p38 did not change. The down regulation of p-ERK and p-JNK was associated with a reduction of Col1 and FN. Similarly, inhibition of ERK and JNK down regulated the expression of Col1 and FN in TGF-β1-stimulated fibroblasts. LB down regulated protein levels of p-ERK and p-JNK in cultured hypertrophic scar tissue ex vivo. Conclusions: This study suggests that LB can inhibit scar formation through the ERK/JNK pathway.

scholarly journals Major cellular events in peripheral nerve regeneration: A brief overview

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Naidu M ◽  
David P
Keyword(s):  
Peripheral Nerve ◽  
Schwann Cells ◽  
Wallerian Degeneration ◽  
Peripheral Nerve Regeneration ◽  
Scar Tissue ◽  
Regenerative Process ◽  
Cellular Events ◽  
Neural Cell Adhesion ◽  
Proximal Stump ◽  
Regeneration Response

Injury to a peripheral nerve leads to degeneration of the segment distal to the site of lesion, a process referred to as Wallerian degeneration. During Wallerian degeneration, axons and myelin sheaths undergo degeneration and are phagocytosed by macrophages and Schwann cells. The Schwann cells proliferate and the endoneurial tubes persist, together the whole structure is known as the band of Büngner. Within few hours, the damaged axons in the proximal stump initiate a regeneration response, with formation of new growth cones. During Wallerian degeneration, neurotrophins, neural cell adhesion molecules, cytokines and other soluble factors are upregulated to facilitate regeneration. The recovery of the target in mammals is often variable, but almost never complete. In humans, scar tissue forms at the site of lesion and this often results in poor recovery of the target. The major events underlying this regenerative process is highlighted and discussed in this review.

scholarly journals 5-Fluorouracil-Loaded Transfersome as Theranostics in Dermal Tumor of Hypertrophic Scar Tissue

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Z. Zhang ◽  
X. Wang ◽  
X. Chen ◽  
Y. Wo ◽  
Y. Zhang ◽  
...  
Keyword(s):  
High Performance ◽  
Scar Tissue ◽  
Hypertrophic Scars ◽  
Transdermal Drug Delivery System ◽  
Permeation Studies ◽  
Fluorescent Agent ◽  
Hypertrophic Scar Tissue ◽  
Laser Confocal Microscope

To investigate the ability of transfersomal gel carrying the antiscarring agent (5-FU) to permeate hypertrophic scarsin vivoandin vitro, scar permeation studies were performed after the agent was labeled with the fluorescent agent, rhodamine 6GO. Laser confocal microscope was employed to dynamically observe the effects of transfersomal gel carrying 5-FU at different time points. High-performance liquid chromatography (HPLC) was used to analyze the contents of the agent in the scar tissues at different hours after administration. Scar elevation index (SEI) was used to evaluate the changes of the ear scar models in rabbits. Compared with the PBS gel of 5-FU, the transfersomal gel displayed greater permeation rate and depth, as well as a higher content retention of the agent in scar tissues. Local administrations of the agent for some certain periods effectively inhibited the hyperplasia of ear scars in rabbits. Transfersomes can be chosen as a potential transdermal drug delivery system.

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